“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.

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.

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

Among them will be Beth Israel Deaconess Medical Center (BIDMC) neuroscientist Lindsay Oberman, PhD, using noninvasive brain stimulation and neuroimaging tools to study the brain in children and adults with autism spectrum disorders.

“The work that Lindsay will be pursuing has the potential to impact the lives of many individuals with these devastating disorders, as well as the lives of their families,” explains Alvaro Pascual-Leone, MD, PhD, Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC and Oberman’s Harvard Catalyst mentor. “This MeRIT program support enables junior scientists to advance their research so that they can reach the next level as clinical and translational scientists.”

Oberman uses transcranial magnetic stimulation (TMS) to probe brain plasticity in ASD patients. TMS is a noninvasive technique in which a magnetic field is generated through a flat “paddle” placed against a patient’s scalp. The painless procedure results in the induction of electric currents and enables Oberman to target small areas of the brain to either enhance or reduce activity and measure the effects on subjects’ neural circuitry.

“Plasticity refers to changes in the brain that stem from new experiences, such as studying a new language or any other learning experience,” explains Oberman, who is also an Instructor of Neurology at Harvard Medical School. “In patients with ASD, we think that these mechanisms of plasticity are abnormally high or ‘hyperplastic.’

“Our research is demonstrating that in individuals with no evidence of autism, these changes in the brain last about 30 minutes,” she explains. But, she adds, among adults with ASD, the brain changes last much longer, 90 minutes on average.

“This suggests that for ASD patients any new experiences are causing lasting brain changes, thereby leading to the communication and social deficits that often characterize these conditions,” says Oberman.

In addition, hyperplasticity may also explain some savant abilities demonstrated by some ASD patients; in such instances, patients are extremely gifted in one area, such as musical ability, in contrast to their overall developmental limitations. But, adds Oberman, on balance, it appears that hyperplasticity results in more problems than benefits for these individuals.

“If our studies in children are consistent with the data we’ve gathered from our adult research subjects, we may eventually be able to use hyperplasticity as a means of diagnosing autism in young children, before the onset of behavioral symptoms,” explains Oberman.

http://www.bidmc.org/News/InResearch/2010/January/LindsayOberman.aspx

In particular, of the 29 cytokine levels investigated, the researchers found disturbed levels in five related to the T-helper cell immune system and three involved in hematopoiesis or the production of blood cells possibly affecting antibody production required for normal functioning of the immune system.

Both the immune system and genetic factors have been implicated in the biological basis for autism, said Merlin G. Butler, professor of psychiatry at the KU Medical Center. “Our study further supports a disturbed immune system in children with classic autism that may be related to genetic factors as cytokine proteins are coded by genes distributed among the human chromosomes.”

Additionally, studies in families with autism have shown the significant contribution of genetics, including deletions and duplications of chromosomes and mutations or variants found in specific genes involved with brain development and function, he said.

“The importance of identifying early immunological disturbances that may contribute to autism has implications for identifying risk factors, diagnosis and possibly intervention as cytokines may play a role in the function of the developing brain,” he said.

The study was one of the largest of its kind to date, analyzing the plasma of 99 children with AD between 5 and 10 years of age and that of 40 age- and gender- matched unrelated healthy siblings without AD under the same clinical assessments, specimen processing and laboratory conditions. The male-to-female ratio closely matches that seen in the ASD population, and there were gender-based differences found in five cytokines.

Butler said that the purpose of this research is linking the genes encoding immune-related proteins and cytokines to ASD along with identifying the sequence of the events during critical periods of brain and neurological development. This could allow for earlier recognition, diagnosis and potential treatment.

Ann Manzardo, assistant professor of psychiatry, was the first author on the study. The study was published in the April 2012 International Journal of Developmental Neuroscience.

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.

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.

Tammy Movsas, M.D., a postdoctoral epidemiology fellow at Michigan State University.

Researchers at Michigan State University have discovered a connection between length of pregnancy and the severity of autism symptoms.

The 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.

Researchers also say that children with autism who were born either preterm or post-term are more prone to self-injury compared with children with autism who are born on time.

The research appears online in the Journal of Autism and Development Disorders.

While it is not yet clear why there is an increase in symptoms of autism, Tammy Movsas, M.D., a postdoctoral epidemiology fellow, believes the reasons may be tied to some of the underlying causes of why a child is born preterm (prior to 37 weeks) or post-term (after 42 weeks) in the first place.

“We think about autism being caused by a combination of genetic and environmental factors,” she said. “With preterm and post-term babies, there is something underlying that is altering the genetic expression of autism.”

“The outside environment in which a preterm baby continues to mature is very different than the environment that the baby would have experienced in utero. This change in environment may be part of the reason why there is a difference in autistic severity in this set of infants.”

Researchers utilized an online database compiled by Kennedy Krieger Institute at Johns Hopkins University of nearly 4,200 mothers — with children with ASD ages 4-21 — between 2006 and 2010. It divided the data on births into four categories: very preterm (born prior to 34 weeks); preterm (34 to 37 weeks); standard (37 to 42 weeks); and post-term (born after 42 weeks).

The mothers were required to complete a pair of questionnaires regarding the symptoms of their children, and the results revealed very preterm, preterm and post-term children with autism had significantly higher screening scores for autism spectrum disorder than those born full term.

“The findings point to the fact that although autism has a strong genetic component, something about pregnancy or the perinatal period may affect how autism manifests,” said Nigel Paneth, M.D., an MSU epidemiologist who worked with Movsas on the paper.”

“This adds to our earlier finding that prematurity is a major risk factor for autism spectrum disorder and may help us understand if anything can be done during early life to prevent or alleviate autism spectrum disorder.”