Infant's Gaze May be Early Mark of Autism Research findings show subtle differences that parents and professionals may easily overlook Kennedy Krieger Institute announced today study results showing an early marker for later communication and social delays in infants at a higher-risk for autism may be infrequent gazing at other people when unprompted.
The study observed 25 infant siblings of children with autism (high-risk group) and 25 infants with no family history of autism (low-risk group) at six months of age in order to assess cause and effect learning as well as social engagement. Infant siblings of children with autism are considered at high-risk for the disorder, as they are 25 times more likely to develop autism. Researchers at Kennedy Krieger, in collaboration with colleagues at the University of Delaware, created a novel, multi-stimuli social learning task, where infants were seated in a custom chair with an attached joystick within easy reach, a musical toy located to the right and their caregiver on the left. Researchers evaluated how quickly the infant learned that the joystick activated the toy and the infant's level of social engagement with their caregiver. Researchers found that, like the low risk group, the high-risk siblings exhibited typical levels of social gazing when their caregivers actively engaged them, such as pointing at the toy and expressing excitement. However, high-risk sibs spent less time looking to their caregivers and more time fixated on the non-social stimuli (toy or joystick) when the caregiver was not engaging them, which could indicate a disruption in development related to joint attention. Joint attention is often a core deficit for children with autism. "My colleagues and I wanted to create a task that would involve learning something novel and would give babies an opportunity to pay attention to either an object or their caregiver," said Dr. Rebecca Landa, corresponding study author and director of Kennedy Krieger's Center for Autism and Related Disorders. "This study shows that there is a particular vulnerability in high-risk siblings at six months of age. They are not as socially interactive and engaged on their own as their peers, but still respond typically when engaged by their caregivers, making for a subtle difference that could be easily overlooked by both parents and some professionals." The study also showed no evidence of impaired associative learning in the high-risk siblings. Both groups demonstrated cause and effect learning abilities; once the infants learned that pulling the joystick activated the toy, they increased how often they pulled on the joystick to activate the toy's music. This finding supports past research demonstrating that associative learning is a relative strength in older individuals with autism and may help to explain why children with autism respond well to teaching approaches that utilize a predictable reward system when children exhibit desired behaviors. "Babies in both groups of the study learned the multi-stimuli task to the same degree," said Dr. Landa. "While the high-risk siblings are at a higher risk for developing autism later in life, they still have the capacity to learn cause and effect as well as their low-risk peers at this young age." Implications from the overall study findings reveal that like older children, infants at high risk for autism may benefit from frequent exposure to simple cause and effect learning opportunities to aid in their development. For example, Landa recommends using simple songs paired with easy, predictable gestures to promote language and social learning, rather than using electronic toys that children can enjoy and operate without engaging with their peers or caregivers. It is expected that about 20% of the high-risk infants in this study will receive a diagnosis of autism. While participants in this study have not yet reached their third birthday, the age at which the research diagnoses are confirmed, the study findings help to highlight the vulnerability of developing social initiation skills in high-risk infants. This study is the first of its kind, and a follow-up will soon be published from the Center for Autism and Related Disorders at Kennedy Krieger Institute. The research study was supported by grants from the National Institutes of Mental Health. About Autism Autism spectrum disorders (ASD) is the nation's fastest growing developmental disorder, with current incidence rates estimated at 1 in 110 children. This year more children will be diagnosed with autism than AIDS, diabetes and cancer combined, yet profound gaps remain in our understanding of both the causes and cures of the disorder. Continued research and education about developmental disruptions in individuals with ASD is crucial, as early detection and intervention can lead to improved outcomes in individuals with ASD.
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Nanotechnology Breakthrough in Cancer Research
Researchers clear hurdle on path toward gene-therapy treatment for disease.
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| Structure of an adenovirus |
The work provides critical structural information for researchers around the world attempting to modify the adenovirus for use in vaccine and gene-therapy treatments for cancer.
To modify a virus for gene therapy, researchers remove its disease-causing DNA, replace it with medications and use the virus shell, which has been optimized by millions of years of evolution, as a delivery vehicle.
Lily Wu, a UCLA professor of molecular and medical pharmacology and co-lead author of the study, and her group have been attempting to manipulate the adenovirus for use in gene therapy, but the lack of information about receptors on the virus's surface hampered their work.
"We are engineering viruses to deliver gene therapy for prostate and breast cancers, but previous microscopy techniques were unable to visualize the adapted viruses," Wu said. "This was like trying to a piece together the components of a car in the dark, where the only way to see if you did it correctly was to try and turn the car on."
To better visualize the virus, Wu sought assistance from Hong Zhou, a UCLA professor of microbiology, immunology and molecular genetics and the study's other lead author. Zhou uses cryo-electron microscopy (cryoEM) to produce atomically accurate three-dimensional models of biological samples such as viruses. The researchers used cryoEM to create a 3-D reconstruction of the human adenovirus from 31,815 individual particle images.
"Because the reconstruction reveals details up to a resolution of 3.6 angstroms, we are able to build an atomic model of the entire virus, showing precisely how the viral proteins all fit together and interact," Zhou said. An angstrom is the distance between the two hydrogen atoms in a water molecule, and the entire adenovirus is about 920 angstroms in diameter.
Armed with this new understanding, Wu and her group are now moving forward with their engineered versions of adenovirus to use for gene therapy treatment of cancer.
"This breakthrough is a great leap forward," Wu said. "If our work is successful, this therapy could be used to treat most forms of cancer, but our initial efforts have focused on prostate and breast cancers because those are the two most common forms of cancer in men and women, respectively."
The group is working with the adenovirus because previous research has established it as a good candidate for gene therapy as it efficiently delivers genetic materials. The virus shell is also a safe as tests have shown that the shell does not cause cancer, a problem encountered with some other virus shells. The adenovirus is relatively non-pathogenic naturally, causing only temporary respiratory illness in 5 to 10 percent of people.
CryoEM enables such a high-resolution reconstruction of biological structures.
In contrast, with X-ray crystallography (the conventional technique for atomic resolution models of biological structures), researchers must grow crystal structures replicating the sample - and then use diffraction to solve the crystal structure.
This technique is limited due to the difficulty of growing crystals for all proteins, samples for x-ray crystallography need to be very pure and uniform, and crystals of large complexes may not diffract to high resolution.
The study was funded by the National Cancer Institute and the U.S. Department of Defense.
The California NanoSystems Institute at UCLA is an integrated research center operating jointly at UCLA and UC Santa Barbara whose mission is to foster interdisciplinary collaborations for discoveries in nanosystems and nanotechnology; train the next generation of scientists, educators and technology leaders; and facilitate partnerships with industry, fueling economic development and the social well-being of California, the United States and the world.