Study Shows Visual Evoked Potential Is a Promising Tool for Translational Research Into Phelan-McDermid Syndrome and Autism Spectrum Disorders
Researchers at the Seaver Autism Center for Research and Treatment at Mount Sinai have identified specific transient visual evoked potential waveform abnormalities in individuals with Phelan-McDermid syndrome (PMS), proving the method to be an effective, noninvasive technique to gather objective data from a range of individuals, including those who are profoundly affected. The study results were published online July 23 in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP).
A visual evoked potential measures electrical activity in the brain by evoking a brain response to a visual stimulus, such as an alternating checkerboard on a computer screen. Responses are recorded from electrodes that are placed on the scalp and are observed as a reading on an electroencephalogram. Phelan-McDermid syndrome is a rare disorder caused by mutations in the SHANK3 gene and is a leading single-gene cause of autism.
The study results suggest that there is a link between the magnitude of loss of function in the SHANK3 gene and subsequent dysregulation of glutamate, a powerful excitatory neurotransmitter that plays an important role in learning and memory.
“Visual evoked potentials (VEPs) can be collected rapidly, repeated frequently, and are a cost-effective method with strong translational potential across human and animal studies,” said Paige Siper, PhD, Chief Psychologist at the Seaver Autism Center and first author of the publication. “With this approach, the availability of treatments targeting core mechanistic disturbances in Pheland-McDermid syndrome and autism may progress more rapidly, thereby making a significant clinical contribution.”
The data collected from the study also provide information about the underlying neurophysiology of Phelan-McDermid syndrome, offering a noninvasive method to examine excitatory and inhibitory neurotransmission that holds promise for stratification and surrogate endpoints in ongoing clinical trials for Pheland-McDermid syndrome and autism.
The results are based on data from 175 children, including 31 with Phelan-McDermid syndrome, 79 with idiopathic autism, 45 typically developing controls, and 20 unaffected siblings of children with the syndrome. Stimuli included standard and short-duration contrast-reversing checkerboard conditions.
The results show that gene deletion size is significantly correlated with the amplitude of an initial negative peak, thought to reflect excitatory activity—while no significant differences between the typically developing and sibling control groups were identified. Both control groups showed significantly stronger VEPs responses compared to the syndrome group, while a subset of children with idiopathic autism displayed a similar response pattern to the Phelan-McDermid syndrome group.
VEPs will now be examined as a biomarker of Phelan-McDermid syndrome and will measure treatment efficacy in ongoing clinical trials in the syndrome.
About the Seaver Autism Center for Research and Treatment
The Seaver Autism Center is one of the most recognized institutions of its kind in the world because of its ability to translate breakthroughs in the lab to clinical trials that bring cutting-edge treatment to individuals affected by autism and associated neurodevelopmental disorders. We offer compassionate care, including assessment and behavioral health services, to individuals and families, as well as educational and community outreach programs. The Center was founded in 1993 and is located at the Icahn School of Medicine at Mount Sinai. Families come from around the world to seek our services and the expert counsel of our team of scientists, researchers, and clinicians.
For more information, visit: www.seaverautismcenter.org, or find the Seaver Autism Center on Facebook, Twitter and Instagram.
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Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
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