Scientists Discover Possible Way to Prune Extra Synapses In Autism

NrCAM protein may be key to pruning extra synapses and treating autism

There has been a lot of exciting research published in the past few months about the autistic brain and genes. The latest discovery comes from the University of North Carolina School of Medicine, and could lead to the development of new medications and therapies for the treatment of autism spectrum disorders (ASD).

The UNC study, lead by Patricia Maness, PhD and professor of biochemistry and biophysics, found that knocking out the gene NrCAM increases the number of dendritic spines on excitatory pyramidal neurons, which earlier studies have concluded results in too many synaptic connections that have been strongly linked to autism. In plain speak; scientists discovered a gene that influences the development of certain extra connections in the brain that make autistic brains function differently than others.

“Basic science in autism is converging in really exciting ways,” Maness said. “Too many spines and too many excitatory connections that are not pruned between early childhood and adolescence could be one of the chief problems underlying autism. Our goal is to understand the molecular mechanisms involved in pruning and find promising targets for therapeutic agents.” 

This study comes on the heels of a study from Columbia University that found an overabundance of the protein MTOR in mice bred with a rare form of autism. They used a drug to limit the mice’s MTOR, which decreased the dendritic spines, thus pruning the extra synapses, resulting in a significant decrease in the social behaviors associated with autism. This drug causes serious side effects, however, and will not become a viable treatment for autism. Also, the location of MTOR protein inside cells makes it particularly difficult to target. 

It isn’t yet known whether or not NrCAM and MTOR are linked, but Maness is now moving on to determine whether the decreased NrCAM protein can activate the MTOR protein. If so, the NrCAM protein may be a viable target for autism therapy, as it is much more accessible than MTOR. 

The UNC study published in The Journal of Neuroscience found that the NrCAM protein works with two other molecules to form a receptor on the excitatory pyramidal neurons that allows dendritic spines to retract and all those excess synapses can be pruned to allow brain circuits to function properly. 

“There are many genes involved in autism, but we’re now finding out exactly which ones and how they’re involved,” continued Maness. “Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism, but to see if we can improve dendritic spine abnormalities, which may underlie autism.”

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Too Much Copper + Not Enough Zinc = New Autism Biomarker

In the ongoing search for ways to screen for autism beyond behavioral symptoms, a new study has uncovered another potential biomarker for autism spectrum disorders (ASD). The collaboration between Mudanjiang Medical University in China and Norway based researchers has found a potentially significant difference in the ratio of trace minerals copper and zinc in autistic children.

Both zinc and copper are necessary in the body, where zinc needs to be in good and constantly replenishing supply and copper levels should be relatively low as not to overburden the body. By analyzing serum levels of the minerals in Chinese children diagnosed with autism, the researchers found that the autistic children had higher levels of copper and lower levels of zinc than their neurotypical counterparts.

What’s more, the researchers established a zinc/copper ratio common in the autistic subjects of the study that they believe can serve as an important biomarker for further testing in relation to autism. This also reinforces previously reported imbalances in zinc and copper with autism that are linked to metabolic pathways involved with oxidative stress and the binding of metals. While both essential minerals are derived from healthy foods, no dietary recommendations have been made as a result of this study. Further research in these areas is said to be in the works.

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Big Babies At Higher Risk For Autism

While one recent study recently concluded that the size of a baby’s head is not a predictor of autism, research out of Denmark draws a clear correlation between the size of a baby and his risk for developing autism. 

Danish researchers analyzed more than 1.7million birth records, and were startled by just how clear a correlation they found between high birth weight and length and the development of autism. Conversely, the study found that big babies had a lower risk of schizophrenia than small or average sized infants. 

This does not mean that all large babies will develop autism spectrum disorders (ASD), but does indicate a possible link in the genetic factors that influence birth size and those that influence mental development. It may also indicate a relationship between genetic factors of both autism and schizophrenia. 

While this study found that babies just 2cm longer than the Danish average had a 20% higher risk of developing autism, it reinforced findings of a similar study of Swedish births that suggested very large newborns with a birth weight over 9lb14oz had 60% higher risk of developing autism than their average sized peers. 

Premature babies were found to have a higher risk for both autism and schizophrenia, despite their tiny size. 

The Danish researchers theorize that genomic imprinting may influence all variations in birth size and risk of autism or schizophrenia, meaning that the genes inherited from the mother and expressed differently than those inherited by the father during development in the womb. 

“It’s quite likely that these imprints that cause either heavier babies or lighter babies are doing parallel things to the infant brain as it grows up,” said Professor Jacobus Boomsma, of the University of Copenhagen’s department of biology. “Exactly how that works mechanically on a genomic level we have no idea, but that is what the theory predicted and what the evidence here supports

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Brighter Futures for Autistic Youths Grown on Chicago Farm

Transitioning from school to the workplace can be incredibly difficult for people with Autism Spectrum Disorders (ASD). Applying lessons from the classroom to the “real world” can be a stretch for anyone, but autistic people in particular benefit from in-situ work experiences where they can develop the requisite social and job skills to gain and succeed in employment. A new program on an urban farm in Chicago does just that – and does it so well that the National Garden Bureau plans to fund therapeutic gardens nationwide. 

Growing Solutions Farm, a 1.2-acre plot on Chicago’s Near West Side grows vegetables, herbs, and edible flowers in addition to job skills and confidence for autistic young adults. The farm teaches every aspect of farming, from planting to harvesting to cooking what they grow to groups of around 20 students aged 18 to 26. While the students learn agriculture-specific skills, they gain a lot more. 

“This is a vocational farm, so we’re teaching job skills,” explains operations manager Gwenne Godwin. “How to work with others, being on time, how to dress, how to do a resume. Those skills translate to any job. We’re using the medium of agriculture to teach here.” 

They also use the garden and kitchen as an opportunity for sensory exploration, a key component to autism therapy. Students are required to taste and smell everything they harvest and cook.

Students also learn to give back to the community, as 75% of their harvest is donated to local food pantries. 

Growing Solutions Farm is part of the Julie + Michael Tracy Family Foundation’s Urban Autism Solutions program and will be a model for similar programs funded by the National Garden Bureau across the country. With the demand for vocational transition programs for autistic young adults and the growing trend of urban farming, opportunities like this will be sprouting up all over, helping our autistic youths grow a brighter future.

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Millions in new autism funds projected by NIMH

Federal officials announce funding of research projects to determine best ways to deliver services to autistic children, teens, and adults.

The National Institute of Mental Health (NIMH)announced that they are funding 12 research projects to identify the best practices and most effective treatments for autistic people at three key stages of life. This comes on the heels of last summer’s renewal of the Autism CARES act by Congress and last year’s finding of the Interagency Autism Coordinating Committee that access to services is a major issue for families with autistic members. 

“Despite the significant number of people of all ages identified with ASD, access to effective services remains inconsistent at best. Parents are often left to navigate what is available as best they can, and worry for the future as their affected children grow into adulthood,” said Thomas Insel, director of the NIMH. “This research is aimed at testing care strategies, adaptable across communities, in which identification of need and engagement in optimal interventions and services will be standard for all ages.” 

The NIMH will provide $7.9 million in the first year of funding for the projects. Some of those projects will determine how best to identify and diagnose children with autism as early as possible and how to ensure those children are connected with intervention services. Another set of projects will focus on people preparing for the post-high school transition, testing methods to improve school-based service coordination for transition services, build parent advocacy skills, and how to teach transitioning young adults self-regulation and self-determination.  The last set of research projects will examine techniques to help adults with autism develop social skills, gain employment, and achieve independent living. 

Federal officials say the studies are designed to highlight approaches that are effective for individuals with autism spectrum disorders of any ethnic or economic background in addition to strategies at these three key life stages.

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Autistic Mice Go Social

Researchers from the California Institute of Technology published a study Septermber 11 in online journal Cell that has exciting implications for understanding underlying neural circuit dysfunctions in autism. Specifically, the study focused on the part of the brain called the amygdala, which processes emotions. The big discovery: antagonistic neuron populations in mouse amygdala control whether the mouse engages in social or asocial behavior. Many studies have already established that autism in mice correlates with autism in humans. 

Researchers describe the discovery as a “see-saw circuit” because the animals can’t engage in both social behavior and asocial repetitive self-grooming at the same time. Their mission was to find out why. 

The team, led by postdoctoral scholar Weizhe Hong in the laboratory of David J. Anderson, the Seymour Benzer Professor of Biology at Caltech and an investigator with the Howard Hughes Medical Institute, discovered two intermingled, yet distinct neuron populations in the amygdala. One population controls social behavior such as mating, fighting, or social grooming, while the other controlled asocial behavior such as repetitive self-grooming. The social neurons, they found, are inhibitory and release the neurotransmitter GABA, while the asocial neurons are excitatory and release the neurotransmitter glutamate, an amino acid. 

The researchers employed a technique called optogenetics to study the relationship between these two types of cells and their associated behaviors. The neurons were genetically altered to express light-sensitive proteins via microbial organisms. Then, by shining a light on the modified neurons via a tiny fiber optic cable inserted in the brain, the researchers were able to control the activity of the cells and their associated behaviors. 

The researchers were effectively able to switch different behaviors on and off. By shining the light on the social neurons, the mice exhibited social behavior. When this light was turned up, the mice became aggressive. When the light was shone on the asocial neurons, the mice spontaneously started to groom themselves. They were then able to switch off the asocial behavior by switching on the social behavior.

What really surprised the researchers was the way in which these two groups of neurons appear to interfere with each other. The activation of the social neurons inhibited the asocial behavior, while the triggering the asocial neurons inhibited the social behavior; hence the seesaw analogy.

In autism,” Anderson says, “there is a decrease in social interactions, and there is often an increase in repetitive, sometimes asocial or self-oriented, behaviors” — a phenomenon known as perseveration. “Here, by stimulating a particular set of neurons, we are both inhibiting social interactions and promoting these perseverative, persistent behaviors.” 

There have been previous studies that show how disruptions in autism-related genes can change social and asocial behavior, but this study is the first to provide the necessary link between gene activity, brain activity, and social behaviors. Obviously, the goal is not to establish a therapy where autistic people have their neurons genetically altered and then controlled via fiber optic cables, but the understanding of this seesaw circuitry will be necessary in developing future therapies. 

“All of this is very far away,” says Anderson, “but if you found the right population of neurons, it might be possible to override the genetic component of a behavioral disorder like autism, by just changing the activity of the circuits — tipping the balance of the see-saw in the other direction.”

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Earlier Intervention Could Be Key To Beating Autism

One of the few things everyone can agree on with autism is that early intervention with behavioral therapy gives children the best chance at beating developmental delays. Now scientists are trying to determine just how early to intervene and to establish therapies that will work for infants. 

Many children start displaying symptoms of autism such as lack of eye contact and repetitive behavior as early as six months, but diagnosis usually comes after the age of three. The reason: all infants develop at different rates and unless a parent is on the lookout for symptoms of autism spectrum disorders (ASD), they can be easily overlooked at such a young age. 

A new study out of UC Davis MIND Institute conducted a small-scale study to determine the efficacy of therapy on very young children. The study monitored the progress of seven children between the ages of 7 and 15 months who showed signs of autism. The infants and their parents attended weekly therapy sessions, where they learned behavioral modification techniques and exercises they could integrate into their daily lives. 

At 36 months, the results were clear: three of the five children who were expected to develop autism when they were babies displayed no delays or symptoms. One child was diagnosed with mild autism but no developmental delays, and one child developed severe autism.

 

“It was like this beautiful thing happened,” says one parent participant with two older autistic children. Her son didn’t just catch up to his peers, but surpassed them. “This completely helped him. I don’t know what would have happened (otherwise).”

Of course, this study was way too small to draw any real conclusions, so why is it getting so much attention? 

Dr. Jeremy Veenstra-VanderWeele, an associate of psychiatry at Columbia University, answers,“This pilot study suggests that parents can be trained to interact with their at-risk infants using many of the same principles that are used for toddlers and preschoolers with ASD.”

“It begins to set the scene for future randomized, controlled studies to evaluate whether this type of intervention could actually prevent babies from developing full symptoms of autism spectrum disorder,” Veenstra-VanderWeele said. If it proves to work on a larger group, this “would be a truly transformative finding.”

It also shows the need to develop methods for earlier diagnosis. As of now, doctors and parents rely on looking for behavioral symptoms that are easily dismissed or overlooked in very young infants, but soon they may be able to screen with genomic testing or even a simple blood test.

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Opposite Brain Activity in Autism and ADHD

The ‘Rich Club Network’ Integrates Information from Different Parts of the Brain

Many children who display hyperactive or inattentive behavior are diagnosed with both Autism Spectrum Disorders (ASD) and attention deficit hyperactivity disorder (ADHD). A new study published last month in Human Brain Mapping, however, suggests the two disorders may be the result of distinctly different, opposing patterns of brain activity.

While ASD and ADHD share some common genetic risk factors and behavioral symptoms, this study looked at the dense network of neural connections that integrates information from different parts of the brain, referred to as the ‘rich club network’. It is believed this rich club may make it possible to accomplish highly complex ordinary tasks, like driving, that require the integration of information from different senses, cognitive ability, and motor skills.

The scientists mapped the long paths of neurons across the brains of 16 autistic children, 20 with ADHD, and 20 controls. They examined which neurons worked in sync while the brains were at rest and combined the structural and functional data, revealing the rich club network by identifying the most highly connected regions of the brain.

It was found that the children with autism tended to have a disorganized rich club network of neurons with an abundance of weak connections. The children with ADHD were shown to have much fewer connections than either the autistic or control group.  Because this study focused on a rather small sampling, the researchers examined data of 85 people with autism and 101 controls stored in the Autism Brain Imaging Data Exchange, and found very similar results.

There have been many studies recently about people with autism, synapses, and brain activity, with apparently inconsistent results at first glance. Some studies show that people with autism have weaker local neurological connections than those without, while others indicate that autism may be the result of too many local connections and not enough long-distance ones. This new study, however, finds a possible middle ground – excess local connections (not necessarily stronger or more functional), but only within the rich club networks.

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Autism Screening – The Latest

With autism diagnosis rates increasing by large margins throughout the US, as well as internationally, researchers are focused on finding ways to screen for symptoms of autism at earlier ages, enabling children to receive the early intervention treatments that they need.

A new study, published today, focuses on studying infants as young as six months old. These children received various forms of therapy, administered by their parents, up to the age of four. By the time these children reached that age, none of them required any additional form of autism therapies or treatments.

Researchers at the University of California Davis MIND Institute focused on infants between the ages of 6 and 15 months, and although they were too young to receive an autism diagnosis, they were labeled at high risk due to severity of specific symptoms. Sally Rogers, professor of psychiatry at US Davis and co-author of the study, states, “We know that autism affects children very differently from one child to another, and we know that no one intervention will affect all children the same.” She continues, “but we do believe, and the infant literature tells us, that learning happens the most rapidlyearly in life, giving less time for the behaviors associated with autism to develop.”

Previous studies focused on children at slightly older stages, primarily between the ages of 18 to 30 months old. These children received 20 hours a week of social and behavioral therapies with clinicians, along with an additional 5 hours of therapy with their parents. The group that received the therapy was observed to have greater improvements in their behavior and capabilities than that of the control group. This study provided strong evidence that intensive early intervention can significantly improve behavior in children on the autism spectrum.

The new study, administered to children much younger, was actually of a low-intensity, and of a low-cost. The focus of the study was to get parents into the habit of interacting with their child from a new perspective.  For example, if babies had difficulties with repetitive hand behaviors, the parents were taught to give their child a toy whenever they began the repetitive motion, to occupy that hand with a stimulating activity. In addition, therapists taught parents to find every opportunity to present themselves directly in their babies’ field of vision, particularly if those babies never sought eye contact.

The study showed that most children were doing very well by the time they reached the age of two, with many no longer qualifying for additional behavioral therapy. Furthermore, many were able to go on to attend a standard preschool. The outcome of this study shows that infant screening is incredibly beneficial, as it can allow for more effective and less intensive interventions.

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Technology Startup Enables Teens with ASD to Prepare for Presentations

In recent years, developments in technology have enabled individuals on the autism spectrum to learn more effectively, communicate better, as well as develop a wide range of skills. Furthermore, advocates and entrepreneurs have made strides to give those with autism better opportunities to live successful lives, including preparing them for employment.

Danielle Feerst, CEO of AutismSees, is dedicated to helping those on the autism spectrum make successful public presentations. AutismSees is a startup that creates technology, specifically apps for mobile devices and tablets, to help those on the spectrum learn how to best present themselves to others and get their message across.

The first app that Feerst has made available is iPresentWell. Although it is fully functional at its current stage, Feerst and her team aim to add more functionality, such as user eye contact and facial recognition tracking. The apps have been backed by various fundraisers, and the team hopes to bring more attention and funding to AutismSees to increase the capabilities of their technology. Feerst states, “We are hoping to gather user feedback and design feedback with our summer trial partner, Goodwill of Silicon Valley. Goodwill is piloting a program to hire and train youth with higher functioning ASD in job interviews and social skills that they are rolling out this summer. So we have kept in contact with them and are developing a new interactive web application and feature changes for our iOS app this fall.  All money we raise on Seedkicks – AutismSees will go to our development and fall research at Tufts University.

Currently, iPresentWell enables users to import a written script of an oral presentation to their device, as well as monitor their eye movement as they reh
earse their presentation, and even record videos as they present. The app also enables users to set goals for themselves, by measuring their progress and seeing their improvements.

AutismSees was founded to be a tech solution to a common issue amongst those on the autism spectrum, which is a lack of eye contact. Large numbers of teens on the spectrum are graduating high school and need tools to prepare themselves for interviews and the transition into the workforce. AutismSees instills confidence by enabling users to practice open-ended dialogue, presentations, debates, and even gives information on how to build professional relationships.

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