Autism Genome Project delivers genetic discovery

A new study from investigators with the Autism Genome Project (AGP), the world's largest research project on identifying genes associated with risk for autism, has found that the comprehensive use of copy number variant (CNV) genetic testing offers an important tool in individualized diagnosis and treatment of autism.

Funded primarily by Autism Speaks, the world's leading autism science and advocacy organization, the Autism Genome Project (AGP) involved more than 50 research centers in 11 countries.

The report, published today in the American Journal of Human Genetics, delivers on the 10-year project's objective to provide practical methods for earlier diagnosis and personalized treatment of autism.

Rob Ring

"With the publication of this study, we should step back to recognize and celebrate the pioneering achievements of the AGP and what they have accomplished in helping to launch the field of genomic risk discovery in autism," says Autism Speaks Chief Science Officer Rob Ring.

"The AGP has generated information that holds the potential to guide medical care for certain individuals with autism today."

"They have demonstrated that science can work for families, and Autism Speaks is proud to have been a supporter of the work all along the way."

The study involved CNV testing of 2,446 families affected by autism and 4,768 individuals unaffected by neurologic or psychiatric disorders.

Overall, CNV s were significantly more common in the participating families affected by autism and, the CNV testing uncovered dozens of cases where autism-linked gene changes were associated with additional health risks warranting medical attention.

In nine of the families affected by autism, CNV s involved a gene that indicates elevated risk for seizures and epilepsy.

Stephen Scherer

"This result warrants an immediate referral to a neurologist," explains senior author Stephen Scherer of the Toronto's Hospital for Sick Children and the University of Toronto.

Similarly, CNV  testing indicated a high risk for Duchene muscular dystrophy in several of the autism families and identified syndromes associated with heart problems in others.

CNV s are genetic changes that involve duplication or deletion of entire segments of DNA.

They do not typically show up on standard genetic tests which search for "spelling mistakes" in the DNA letters that compose a gene.

Those standard tests identify a clear genetic autism link in only 15 to 20 percent of the cases.

"This report and its extensive supplements should become a new guidebook for medical geneticists working with families affected by autism," Dr. Scherer says.

In addition, the study added dozens of genes to the growing list of those that contribute to the development of autism.

Surprisingly, the autism genes identified through CNV testing had little overlap with those detected using standard exome gene sequencing, yet researchers say they affect the same brain pathways.

"These gene discoveries will help guide further research on autism subtypes and their treatment," Dr. Scherer says.

In response, the investigators urge medical geneticists to add CNV testing to the standard gene tests for autism and to consult medical recommendations for the many autism-linked syndromes that CNV testing can reveal.

CNV testing is currently available, though it's not typically part of standard genetic testing for autism.

Whole genome sequencing is the next step in genetic testing for Autism but is not yet widely available in ordinary medical settings.

Autism Speaks has taken a world-leadership position in in this direction with its Autism Ten Thousand Genomes (Aut10K) program.

More Information: "Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders" American Journal of Human Genetics: ((2014), doi.org/10.1016/j.ajhg.2014.03.018

Making your child into an Accomplished Liar

A primary rule for parents when dealing with lying is don't badger or corner children! Imagine you give a child the third degree about whether or not she has homework.

She denies it six times and finally, after your seventh question, she admits that, Yes, she has some.

What has happened?

By this time, of course, you are furious. More important, however, you also have given your child six times to practice lying!

You may think to yourself, "Sooner or later she'll realize she can't fool me and she'll give up." Wrong. Many children will continue to take the easy way out: they will simply attempt to avoid any confrontation with you and become better liars.

Either You Know the Truth or You Don’t
Look at it this way: you either know the truth or you don't. If you don't know what is going on, ask once and don't badger.

It's a good idea here not to ask "impulsively”.

Many kids simply respond back impulsively. They lie, but their real desire is just to end the conversation, get rid of you, and avoid trouble.

If you are going to ask, you might say something like, "I want you to tell me the story of what happened, but not right now. Think about it a while and we'll talk in fifteen minutes."

If she tells you the story and you find out later that the child lied, punish her for whatever the offense was as well as for the lie. No lectures or tantrums from you.

Deal with the problem and try to fix things, as best you can, so that lying does not seem necessary to the child.

If you do know what has happened, tell her what you know and deal with it. If she has done something wrong that you know about, simply punish her reasonably for that and end the conversation with, "I'm sure you'll do better next time."

Keep Your Perspective
Some parents still prefer to ask a child what happened, even when they already know what it was. This is OK if you do it right.

You should say something like, "I got a call from the school today about an incident at lunch. I'm going to ask you to tell me the story, but not right now. I want you to think about it for a while, and then when you're ready you can tell me, but remember I already pretty much know what happened."

Lying is not good, but it certainly isn't the end of the world either. It happens from time to time. It doesn't mean that your kids don't love you or that they are bound to grow up to become professional criminals.

However, over time, frequent emotional overreactions on your part, combined with badgering and cornering, can produce a very Accomplished Liar.

ADHD: Language problems common in children with ADHD

Children who have attention-deficit/hyperactivity disorder are nearly three times more likely to have language problems than kids without ADHD, according to new research.

And those language difficulties can have far-reaching academic consequences, the study found.

The study, published online April 21 in Pediatrics, looked at 6- to 8-year-olds with and without ADHD in Australia.

"We found that 40 percent of children in the ADHD group had language problems, compared to 17 percent of children in the 'control' group," said Emma Sciberras, a clinical psychologist and post-doctoral research fellow at the Murdoch Children's Research Institute in Victoria, Australia.

"Rates of language problems were similar in boys and girls with ADHD," she added.

Emma Sciberras

Children with ADHD commonly have trouble with school performance and social functioning.

The impact that language problems might have on these factors hasn't been well-studied, the study authors noted.

"The differences in academic functioning between children with ADHD and language problems, compared to those with ADHD alone, were quite large and clinically meaningful," said Sciberras.

Language problems refer to spoken language—both receptive and expressive language. Receptive language is the ability to listen and understand what's being said; expressive is the ability to speak and be understood.

In a separate study in the same issue of the journal, Sciberras and her colleagues looked at almost 400 children with ADHD, aged 5 to 13, and found almost two-thirds had one or more anxiety disorders.

When children with ADHD had two or more anxiety disorders—this was true for one-third of the kids—their quality of life, behavior and daily functioning suffered, the researchers said.

"It is very common for children with ADHD to experience additional difficulties," said Sciberras. "Both of these studies demonstrate that the additional difficulties that go along with ADHD, in this case anxiety and language problems, can make daily functioning even harder for children with ADHD."

The language study included 179 children diagnosed with ADHD and 212 without the attention disorder. Fewer than half of the children with ADHD were taking medications to help control their symptoms.

After adjusting for sociodemographic factors and other conditions, such as autism spectrum disorders, the researchers found that the risk of language problems was 2.8 times higher in children with ADHD.

When the researchers looked at how those language problems affected school work, they found lower math, reading and academic scores.

However, the researchers didn't find that language problems had an impact on social functioning.

"We were surprised that language problems were not associated with poorer social functioning for children with ADHD," Sciberras said.

"It could be that children with ADHD are already experiencing poorer social functioning due to other factors including their ADHD symptoms or other associated difficulties."

However, Sciberras cautioned that language troubles might become more problematic as these kids get older because social relationships get more complex with age.

One outside expert said the study is a good reminder for parents and physicians.

Bradley Berg

"If a child has ADHD and they're struggling in school, even though their ADHD symptoms are well-controlled, in addition to getting tested for learning disabilities, they should also be looked at for language difficulties as well. And that's not something we always think of," said Dr. Bradley Berg, medical director of McLane Children's Pediatrics at Baylor Scott & White Healthcare in Round Rock, Texas.

Whether speech-language interventions will help the youngsters with ADHD isn't clear, however.

Berg also pointed out that this issue is a "chicken-and-egg" problem.

He said "We don't know if these kids have;

• a language disorder that's causing them to not understand what's going on at school 
• and that's making them restless and fidgety because they're bored
• Or do they have ADHD and that's causing difficulty understanding the language. 
• Or is there something going on in an area of the brain that creates both of these problems?

It's possible that the findings from this Australian study might not translate to a U.S. population.

For one thing, medication trends might differ, Berg said. For children with ADHD who also suffer anxiety, Sciberras said medications might help, and a type of psychotherapy called cognitive behavioral therapy could also be useful.

The researchers are currently conducting a study to treat anxiety in children with ADHD.

"If parents are concerned that their child with ADHD has anxiety, language or any other additional difficulties that are not currently being managed, we encourage them to discuss their concerns with their child's treating clinician," she said.

Dyslexia : Perception Poster

Autism: Diagnosis and Treatment

In the US April is National Autism Awareness Month.

The Child Development Clinic at Children's Hospital of Richmond at VCU (CHoR) provides comprehensive assessment for pediatric patients with developmental delays or disabilities, including those with autism spectrum disorders.

The medical, psychological, social work and educational testing offered by the clinic leads to a diagnosis and recommendations to help patients and their health care providers with care planning, referrals, follow-up care coordination and treatments.

Pasquale Accardo

We sat down with Pasquale Accardo, M.D., professor and chief of the Division of Developmental Pediatrics at CHoR, to learn more about autism, including symptoms, diagnosis and treatment.

What is autism?

Autism is a neurodevelopmental disorder, this means that it is a chronic brain problem, a difficulty that the brain has with processing certain kinds of information.

In the case of autism, typically the greatest difficulty is dealing with social interaction.

What are the common signs and symptoms of autism?

Common signs of autism vary with age:

• Young children often first present with language issues.
• Preschool and school-age children often exhibit attention deficit hyperactivity disorder (ADHD) symptoms and other challenging behaviours.
• Older children have significant socialization problems, repetitive and obsessive compulsive behaviours.

Symptoms of autism do change with time; certain delays are more common in younger children whereas socialization and processing problems are more common in older children and adults.

How is autism diagnosed?

Autism is diagnosed using a variety of approaches:

• A clinical history and examination may be sufficient.
• Formal testing can include a variety of questionnaires, including the Gilliam Autism Rating Scale, now in its 3rd edition (GARS-3) and the Childhood Autism Rating Scale, now in its 2nd edition (CARS-2) administered to the parents and teachers.
• Autism Diagnostic Observation Schedule (ADOS) testing is considered the gold standard.

How is autism treated?

Autism is best treated with a variety of Early Intensive Behavioural Interventions (EIBI); speech language therapy and occupational therapy can also be used.

Applied Behaviour Analysis (ABA) is considered the standard for behavioral intervention, but most other effective behavioral programs are variants on ABA.

Autism: Parents advised to get a dog

Many families face the decision of whether to get a dog.

For families of children with autism, the decision can be even more challenging.

Now, a University of Missouri researcher has studied dog ownership decisions in families of children with autism and found, regardless of whether they owned dogs, the parents reported the benefits of dog ownership included companionship, stress relief and opportunities for their children to learn responsibility.

"Children with autism spectrum disorders often struggle with interacting with others, which can make it difficult for them to form friendships," said Gretchen Carlisle, a research fellow at the Research Center for Human-Animal Interaction (ReCHAI) in the MU College of Veterinary Medicine.

"Children with autism may especially benefit from interacting with dogs, which can provide unconditional, nonjudgmental love and companionship to the children."

Carlisle interviewed 70 parents of children with autism. Nearly two-thirds of the parents in the study owned dogs, and of those parents, 94 percent reported their children with autism were bonded to their dogs.

Even in families without dogs, 70 percent of parents said their children with autism liked dogs.

Many dog-owning parents said they specifically chose to get dogs because of the perceived benefits to their children with autism, Carlisle said.

"Dogs can help children with autism by acting as a social lubricant," Carlisle said. "For example, children with autism may find it difficult to interact with other neighbourhood children."

"If the children with autism invite their peers to play with their dogs, then the dogs can serve as bridges that help the children with autism communicate with their peers."

Parents of children with autism should consider their children's sensitivities carefully when choosing a dog in order to ensure a good match between pet and child, Carlisle said.

"Bringing a dog into any family is a big step, but for families of children with autism, getting a dog should be a decision that's taken very seriously," Carlisle said.

"If a child with autism is sensitive to loud noises, choosing a dog that is likely to bark will not provide the best match for the child and the family."

"If the child has touch sensitivities, perhaps a dog with a softer coat, such as a poodle, would be better than a dog with a wiry or rough coat, such as a terrier."

Carlisle recommends parents involve their children with autism when choosing a dog.

"Many children with autism know the qualities they want in a dog," Carlisle said. "If parents could involve their kids in choosing dogs for their families, it may be more likely the children will have positive experiences with the animals when they are brought home."

Although her study only addressed dog ownership among families affected by autism, Carlisle said dogs might not be the best pet for every child with autism.

"If you know one child with autism, you know one child with autism," Carlisle said. "Dogs may be best for some families, although other pets such as cats, horses or rabbits might be better suited to other children with autism and their particular sensitivities and interests."

"This research adds scientific credibility to the benefits of human-animal interaction," said Rebecca Johnson, a professor at the MU College of Veterinary Medicine, director of ReCHAI, and the Millsap Professor of Gerontological Nursing in the MU Sinclair School of Nursing.

"This research helps us understand the role of companion animals in improving the lives of children with autism and helps health professionals learn how to best guide families in choosing pets for their families."

The study, "Pet Dog Ownership Decisions for Parents of Children With Autism Spectrum Disorder," was published in the Journal of Pediatric Nursing earlier this year.

SIDS: New insight into cot deaths points to lack of oxygen

Research at the University of Adelaide has shed new light onto the possible causes of sudden infant death syndrome (SIDS), which could help to prevent future loss of children's lives.

In a world-first study, researchers in the University's School of Medical Sciences have found that telltale signs in the brains of babies that have died of SIDS are remarkably similar to those of children who died of accidental asphyxiation.

"This is a very important result. It helps to show that asphyxia rather than infection or trauma is more likely to be involved in SIDS deaths," says the leader of the project, Professor Roger Byard AO, Marks Professor of Pathology at the University of Adelaide and Senior Specialist Forensic Pathologist with Forensic Science SA.

The study compared 176 children who died from head trauma, infection, drowning, asphyxia and SIDS.

Researchers were looking at the presence and distribution of a protein called â-amyloid precursor protein (APP) in the brain.

This "APP staining", as it's known, could be an important tool for showing how children have died. This is the first time a detailed study of APP has been undertaken in SIDS cases.

"All 48 of the SIDS deaths we looked at showed APP staining in the brain," Professor Byard says.

"The staining by itself does not necessarily tell us the cause of death, but it can help to clarify the mechanism.

"The really interesting point is that the pattern of APP staining in SIDS cases - both the amount and distribution of the staining - was very similar to those in children who had died from asphyxia."

Professor Byard says that in one case, the presence of APP staining in a baby who had died of SIDS led to the identification of a significant sleep breathing problem, or apnoea, in the deceased baby's sibling.

"This raised the possibility of an inherited sleep apnoea problem, and this knowledge could be enough to help save a child's life," Professor Byard says.

"Because of the remarkable similarity in SIDS and asphyxia cases, the question is now: is there an asphyxia-based mechanism of death in SIDS? We don't know the answer to that yet, but it looks very promising."

This study was conducted at the University of Adelaide by visiting postdoctoral researcher Dr Lisbeth Jensen from Aarhus University Hospital, Denmark, and was funded by SIDS and Kids South Australia.

The results have been published in the journal Neuropathology and Applied Neurobiology.

"This work also fits in very well with collaborative research that is currently being undertaken between the University of Adelaide and Harvard University, on chemical changes in parts of the brain that control breathing," Professor Byard says.

ADHD/ADD: Confirmation of the neurobiological origin

In this image, marking shows the axons in retinal neurons (in red) that innervate the superior colliculus (in blue) in a "normal" mouse. 

Credit: Michael Reber / Institut des Neurosciences Cellulaires et Intégratives 

A study, carried out on mice, has just confirmed the neurobiological origin of attention-deficit disorder (ADD), a syndrome whose causes are poorly understood.

Researchers from CNRS, the University of Strasbourg and INSERM have identified a cerebral structure, the superior colliculus, where hyperstimulation causes behaviour modifications similar to those of some patients who suffer from ADD.

Their work also shows noradrenaline (Norepinephrine) accumulation in the affected area, shedding light on this chemical mediator having a role in attention disorders.

These results are published in the journal Brain Structure and Function.

Attention-deficit disorder (ADD/ADHD) affects between 4-8% of children. It manifests mainly through disturbed attention and verbal and motor impulsiveness, sometimes accompanied by hyperactivity.

About 60% of these children still show symptoms in adulthood. No cure exists at this time. The only effective treatment is to administer psychostimulants, but these have substantial side effects, such as dependence.

Persistent controversy surrounding the neurobiological origin of this disorder has hindered the development of new treatments.

The study in Strasbourg investigated the behaviour of transgenic mice having developmental defects in the superior colliculus.

This structure, located in the midbrain, is a sensory hub involved in controlling attention and visual and spatial orientation.

The mice studied were characterized by duplicated neuron projections between the superior colliculus and the retina. This anomaly causes visual hyperstimulation and excess noradrenaline in the superior colliculus.

The effects of the neurotransmitter noradrenaline (Norepinephrine), which vary from species to species, are still poorly understood.

However, we do know that this noradrenaline (Norepinephrine) imbalance is associated with significant behavioural changes in mice carrying the genetic mutation.

By studying them, researchers have observed a loss of inhibition: for example mice hesitate less to penetrate a hostile environment.

They have difficulties in understanding relevant information and demonstrate a form of impulsiveness. These symptoms remind us of adult patients suffering from one of the forms of ADD.

Currently, the fundamental work on ADD uses mainly animal models obtained by mutations that disturb dopamine production and transmission pathways. In mice with a malformed superior colliculus, these pathways are intact.

The changes occur elsewhere in the neural networks of the midbrain. By broadening the classic boundary used to research its causes, using these new models would allow a more global approach to ADD to be developed.

Characterising the effects of noradrenaline (Norepinephrine) on the superior colliculus more precisely could open the way to innovative therapeutic strategies.

More information: Chantal Mathis, Elise Savier, Jean-Bastien Bott, Daniel Clesse, Nicholas Bevins, Dominique Sage-Ciocca, Karin Geiger, Anaïs Gillet, Alexis Laux-Biehlmann, Yannick Goumon, Adrien Lacaud, Vincent Lelièvre, Christian Kelche, Jean-Christophe Cassel, Frank W. Pfrieger, Michael Reber. "Defective response inhibition and collicular noradrenaline enrichment in mice with duplicated retinotopic map in the superior colliculus." Brain Structure and Function, 2014; DOI: 10.1007/s00429-014-0745-5

Bullying affects most Adolescents, Popularity Increases the Risk of Getting Bullied

Bullying affects more than just those children who are seen to be isolated and marginalised, according to sociologists.

In fact, researchers have found that the 'popular' students are affected and may actually suffer more from a single act of social aggression.

"We did find that students who are isolated do get bullied," said Diane Felmlee, professor of sociology, Penn State.

Diane Felmlee

"However, for most students, the likelihood of being targeted by aggressive acts increases as a student becomes more popular, with the exception of those at the very top."

In a study of students and their friendship networks in 19 North Carolina schools, the researchers found that the risk of being bullied drops dramatically only for the adolescents in the top five percent of the school's social strata.

Bullying may be a tactical form of aggression, according to the researchers, who report their findings in the current issue of American Sociological Review (pdf).

Young people who are attempting to climb in status may increase their risk of victimization.

Robert Faris

"When youth are vying for status, they probably gain little from attacking students who are already marginalised, in fact, it might backfire," said Felmlee, who worked with Robert Faris, associate professor, University of California Davis.

"But, if adolescents put down someone who is trying to be a leader in their group, or who constitutes a threat to their status, then there is a lot more to be gained."

Faris and Felmlee also found that girls are more likely to be victims of both male and female bullies. Girls who date are at increased risk of physical violence.

"Girls may pose particular threats to other female students' social standing and represent potential rivals when it comes to securing a boyfriend," said Felmlee.

"For boys, girls who date represent rewarding, often popular and relatively easy targets who are unlikely to retaliate physically."

Students who have an aggressive friend tend to avoid being victimized. This may be further evidence that bullying is rarely an individual act, but associated with how friends establish and maintain hierarchies by protecting their own, according to the researchers.

There are serious costs associated with bullying over time, Felmlee said. Victims suffer elevated levels of anxiety, depression and anger. They tend to develop negative feelings about their schools, as well.

Bullying's detrimental effects can be even more pronounced among relatively popular students, according to the researchers.

Higher status students experienced significantly larger increases in depression, anxiety and anger than low-status students.

The friendships of these students also deteriorated.

"The effects of social aggression were magnified by the student's friendship status," said Felmlee.

"It may be that the kids who are extremely popular and rarely victimized had farther to fall than those more accustomed to being a target, so, although socially vulnerable youth suffer significantly from frequent harassment, more central victims of bullying, those who may be 'hidden in plain sight' face serious consequences."

The researchers examined data from the Context of Adolescent Substance Use study, which surveyed about 4,200 middle and high school students twice during the school year.

The surveys included questions on serious verbal and physical harassment, but did not include minor incidents, such as playful teasing.

The students were asked to provide information about their friendships, as well as information about students whom they believe they harassed and about those who they believe harassed them.