PHILADELPHIA — A major international consortium co-led by Penn Medicine has received a $12 million National Institute of Mental Health (NIHM) grant for a large-scale genetics study investigating why patients with chromosome 22q11.2 deletion syndrome have an increased risk of schizophrenia and other psychiatric disorders.
Co-directed by Raquel E. Gur, MD, PhD, director of the Neuropsychiatry Program at the Perelman School of Medicine at the University of Pennsylvania, the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome brings together top researchers and clinicians from 22 institutions, including Penn Medicine and The Children’s Hospital of Philadelphia, and five genotyping sites, across North America, Europe, Australia and South America.
With the four-year grant from the NIMH, part of the National Institutes of Health, the Consortium will study the genetic causes behind the high rates of schizophrenia and other psychiatric disorders in those with deletion syndrome, a multisystem disorder that includes birth defects and developmental and behavioral differences across the life span. Such findings may also help identify pathways leading to schizophrenia in the general population in a way that will inform new treatments.
“The funding from the NIH will provide us with the opportunity to advance the understanding of this under-recognized neurogenetic condition,” said Gur. “The knowledge generated can provide a window to the brain that will benefit millions throughout the world.”
Co-directing the overall consortium with Gur is Donna McDonald-McGinn, M.S., CGC, program director of the “22q and You Center” at CHOP. McDonald-McGinn and Gur, who frequently collaborate on chromosome 22q research, are the principal investigators of the project’s sites at their respective institutions.
Found in approximately 1 in 4,000 live births, 22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body, including heart abnormalities that often require surgery in the newborn period, an opening in the roof of the mouth, trouble fighting infection due to a poorly functioning immune system, seizures due to low calcium, and significant feeding and swallowing issues. In contrast, some individuals with the 22q11.2 deletion have none of these medical issues. However, most children have developmental delays including delayed acquisition of motor milestones, learning disabilities, and significant delays in emergence of language. Moreover, some children have autistic spectrum disorder, ADHD and anxiety.
When entering adolescence or young adulthood, approximately 25 to 30 percent of patients are at risk of developing schizophrenia, much higher than the one percent rate in the general population.
The Consortium sites have extensive experience in applying integrative genomic and brain-behavior strategies to study individuals with deletion syndrome and schizophrenia, and together have provided data on 1,000 genetically and phenotypically characterized individuals with the syndrome, the largest such available sample to date.
“The project is an unprecedented international initiative to examine a common deletion associated with schizophrenia and elucidate its genomic and behavioral substrates,” said Dr. Gur.
CHOP’s McDonald-McGinn added: “Not only does this successful application demonstrate the genuine commitment on the part of the National Institute of Mental Health to better understand the brain and psychiatric illness, but it highlights the need for such international collaborations. In this instance, 22 clinical and 5 basic science collaborating sites, all with extremely dedicated clinicians and researchers who have overcome the challenges of differing cultures, languages, time zones, and healthcare systems, are working toward the common goal of improving patient care and long term outcome.”
In addition to Penn Medicine and the “22q and You Center” at CHOP, participating academic sites in the United States include New York’s Albert Einstein College of Medicine, Duke University, Emory University, SUNY Syracuse, UCLA, and UC Davis; with sites in Canada (Toronto), Europe (Leuven, Belgium; Marseille, France; Dublin, Ireland; Rome, Italy; Utrecht and Maastricht, the Netherlands; Mallorca and Madrid, Spain; Geneva, Switzerland; Cardiff and London, United Kingdom); Tel Aviv, Israel; Australia (Newcastle); and Chile (Santiago).
The NIH grant supporting the Consortium is U01MH101719.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.