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.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.