A new study brings important insights about the cellular and molecular mechanisms involved in the loss and gain of synaptic function in human neurons from patients with Phelan-McDermid syndrome and autism. It also provides encouragement that neurons derived from induced pluripotent stem cells of patients will be useful in understanding and developing treatments for neurodevelopmental and psychiatric disorders.
By Dr. Oleksandr Shcheglovitov
22q13.3 deletion syndrome (also known as Phelan-McDermid syndrome) is a genetic neurodevelopmental disorder characterized by global developmental delay, severely impaired speech, intellectual disability, and autism. The syndrome is caused by the heterozygous microdeletions in the terminal region of chromosome 22. Although, a candidate gene responsible for the neurological abnormalities in patients has been suggested (SHANK3, which encodes a scaffolding protein of excitatory synapses), cellular and molecular defects associated with this syndrome were unknown. In the study published in Nature today, researchers from Stanford University reported that human neurons derived from induced pluripotent stem cells of patients with Phelan-McDermid syndrome and autism have deficits in excitatory synaptic transmission due to reduced number of excitatory synapses. The authors demonstrated that SHANK3 is primarily responsible for these deficits, as neurons from patients had reduced SHANK3 expression and increasing the levels of SHANK3 expression rescued synaptic deficits in patient cells.
The authors also tested several drugs for their ability to increase the number of excitatory synapses in neurons derived from patients and found that prolonged treatment with Insulin Growth Factor 1 (IGF1) completely restores excitatory synaptic transmission in patient cells. Interestingly, IGF1 produced its action by increasing the number of different type of excitatory synapses that express scaffolding protein PSD95 and lack SHANK3 expression.
In summary, this study brings important insights about the cellular and molecular mechanisms involved in the loss and gain of synaptic function in human neurons from patients with Phelan-McDermid syndrome and autism. It also provides encouragement that neurons derived from induced pluripotent stem cells of patients will be useful in understanding and developing treatments for neurodevelopmental and psychiatric disorders.
Researchers have optimized the production from stem cells of large numbers of a subtype of neurons involved in cognitive function. These neurons express the chemical messenger glutamate and are implicated in cognitive disorders such as autism. This technique, published in Translational Psychiatry, could generate enough neurons for large-scale screening of drugs.
Researchers have developed a new test that reveals complex repetitive behaviors in BTBR mice, a mouse strain with features resembling those of autism, according to a study published in the Journal of Neuroscience Methods. Repetitive behavior is common in autism, and usually comes in two forms: repetitive actions, such as hand flapping or rocking, and higher-order symptoms, such as an insistence on sameness, or restricted interests. This second form is difficult to produce in mice, but these researchers believe they have been able to do it.
New research from the CDC and published in the journal Developmental Medicine & Child Neurology found significantly high rates of autism among children diagnosed with cerebral palsy. Of the 147,000 children studied, seven percent of the children with cerebral palsy were also diagnosed with autism, compared to a little greater than one percent of kids who have autism in the general population.
Research published in the American Journal of Human Genetics found that people with ASDs often have just one copy of certain genes, when typically-developing people have two. This "mis-wiring" could alter the activity of nerve cells in the brain. The study found that the most commonly missing genes were linked to autophagy - a kind of waste-disposal and renewal process for cells. This study was led by Dr. Joseph Buxbaum, who is on ASF's Scientific Advisory Board.
Some children with autism show unique patterns of brain activation while solving math problems, particularly in a brain region normally used for face processing, suggests a study in Biological Psychiatry. They also seem to use more sophisticated mental strategies to solve these problems than do their typically developing peers, the researchers found.
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A study published earlier this year in the journal Research in Autism Spectrum Disorders found aggressive behavior in more than half of autistic children and adolescents. These behaviors are notoriously difficult to treat; a 2005 British study confirmed that aggressive and self-injurious behaviors don’t improve as children age—rather, they worsen in intensity and frequency over time.
This symposium will address the treatment of dangerous behaviors, including:
•What types of behaviors are more likely to respond to medical treatments than behavior strategies
•Which medications have been most successful treating these behaviors
•What can be done if medications fail, including ECT and neurobehavioral units
An extensive question and answer session will follow the presentations. A light dinner will be served during the break.
Register online at easifoundation.eventbrite.com. Registrations will be accepted at the door if space permits.
The results of a recent study will probably come as no surprise to most parents of children with autism: children with ASDs have more sleep problems than their peers. In fact, between ages 2.5 and 11.5, kids with autism average 43 fewer minutes of sleep per night when compared to their typically-developing peers. The next step is to research how less sleep may play a part in behavior problems.
Siblings of children with autism who are later diagnosed with the disorder themselves become more active, less adaptable and less likely to approach others over time, according to a study published in the Journal of Autism and Developmental Disorders. The results reinforce the observation that autism symptoms evolve as children age, the researchers say.
A new nationwide study conducted in Sweden and published in JAMA Psychiatry found there to be no link between celiac disease and autism spectrum disorders. There was, however, some evidence that people who have been diagnosed with autism are more sensitive to gluten, even though they don't have celiac disease. The design of the study did not allow for a conclusion that gluten sensitivity caused autism, nor vice versa.