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Upstate is part of International Consortium to share $12M NIH grant

An international collaboration that includes Upstate Medical University will receive $12 million over four years from The National Institute of Mental Health of the National Institutes of Health to study the genetics of schizophrenia and other psychiatric disorders in chromosome 22q11.2 deletion syndrome, a multisystem disorder that includes birth defects and developmental and behavioral differences across the life span.

The International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome is a large-scale effort among 22 institutions across North America, Europe, the Middle East, Australia and South America. Upstate will receive $263,086 for its participation in the study.

Researchers will investigate the genetic causes for the high rates of schizophrenia and other neuropsychiatric disorders, as well as intellectual disabilities, in those who are affected with chromosome 22q11.2 deletion syndrome.

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.

Affected individuals may also have additional medical issues such as breathing problems, kidney abnormalities, scoliosis, and hearing loss.  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 autism or autistic spectrum disorder, ADHD, OCD and anxiety.  Later in life, persons with the 22q11.2 deletion are at an increased risk of developing severe psychopathology, particularly schizophrenia, as well as depression and anxiety disorder. Approximately 25 to 30 percent of adolescents and young adults with 22q11.2 deletion syndrome develop psychotic illness. The illness presentation and course are similar to those of idiopathic schizophrenia, which occurs in the general population at a much lower rate (about 1 percent).

“The funding from the NIH will provide us with an unprecedented opportunity to advance the understanding of this under-recognized neurogenetic condition,” said Upstate’s principal investigator Wendy R. Kates, PhD, professor of psychiatry and behavioral sciences. “The knowledge generated can provide a window to the brain that will benefit millions throughout the world.”

Beyond the potential for yielding a better understanding of a severe manifestation of 22q11.2 deletion syndrome, the results will help identify pathways leading to schizophrenia in the general population in a way that will inform novel treatments.

The consortium sites have extensive experience in applying integrative genomic and brain-behavior strategies to study individuals with 22q11.2 deletion syndrome and schizophrenia across the lifespan, and together have provided data on 1,000 genetically and phenotypically characterized individuals with the syndrome, the largest such available sample to date.

The genomic efforts will include whole-genome sequencing in order to uncover genetic variation that may contribute to the heterogeneity of neuropsychiatric and neurobehavioral phenotypes of schizophrenia and psychosis.

“The project is an unprecedented international initiative to examine a common deletion associated with schizophrenia and elucidate its genomic and behavioral substrates,” said Kates. 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 dedicated clinicians and researchers who have overcome the challenges of differing cultures, languages, time zones, and health care systems, are working toward the common goal of improving patient care and long-term outcome.

The lead site for this study is the University of Pennsylvania.  In addition to the University of Pennsylvania and Upstate, the participating academic sites in the United States include the 22q and You Center at the Children’s Hospital of Philadelphia, New York’s Albert Einstein College of Medicine, Duke University, Emory University, UCLA, and UC Davis; sites outside of the U.S. include 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).

Caption: Wendy Kates, PhD, is heading a study at Upstate Medical University that will look at the genetics of schizophrenia in deletion syndrome patients.

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