A multisystem disorder, Chromosome 22q11.2 deletion syndrome can also include developmental delays 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 involving 22 institutions in North America, including UCLA, as well as several across Europe, Australia and South America. The collaborative effort has been awarded $12 million over four years from the National Institute of Mental Health.
Occurring in approximately one out of every 4,000 live births, 22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. These can include heart abnormalities that often require surgery in newborns, trouble fighting infection due to a poorly functioning immune system, and significant feeding and swallowing issues.
While a few individuals with the syndrome will not experience any ofthese medical issues, the majority of children have developmental delays. These can include delayed acquisition of motor milestones, learning disabilities and significant delays in the emergence of language. Moreover, a substantial number of children with the disorder have autism or autistic spectrum disorder, attention deficit–hyperactivity disorder (ADHD), and/or anxiety disorder.
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).
“This funding from the NIMH will provide us with the opportunity to advance the understanding of this under-recognized neurogenetic condition,” said Carrie Bearden, consortium co-principal investigator, UCLA lead investigator and professor of psychiatry and psychology at UCLA. “Beyond the potential for yielding a better understanding of the genetic causes of the severe manifestations 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. Together, the sites have provided data on 1,000 genetically and phenotypically characterized individuals with the syndrome, the largest available sample to date.
The genomic efforts will include whole-genome sequencing in order to uncover genetic variations 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 Bearden, who is also the director of the UCLA Center for the Assessment and Prevention of Prodromal States, which identifies and treats adolescents and young adults at risk for developing psychotic disorders.
“Not only does this successful application demonstrate the genuine commitment on the part of the NIMH to better understand the brain and psychiatric illness, but it highlights the need for such international collaborations,” she said.
In this instance, said Bearden, 22 clinical and five basic science collaborating sites, all with extremely 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 outcomes.
In addition to UCLA, participating academic sites in the U.S. include the University of Pennsylvania, Children’s Hospital of Philadelphia, New York’s Albert Einstein College of Medicine, Duke University, Emory University, SUNY Syracuse and UC Davis. Other sites are located in Toronto, Canada; 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; Newcastle, Australia; and Santiago, Chile.
The UCLA Department of Psychiatry and Biobehavioral Sciences is the home within the David Geffen School of Medicine at UCLA for faculty who are experts in the origins and treatment of disorders of complex human behavior. The department is part of the Semel Institute for Neuroscience and Human Behavior at UCLA, a world-leading interdisciplinary research and education institute devoted to the understanding of complex human behavior and the causes and consequences of neuropsychiatric disorders.