Combined MR Imaging and Genetics Study Provides Clues into Childhood Obsessive-Compulsive Disorder

This project, funded by the U.S. National Institute of Mental Health at the National Institutes of Health (Bethesda, MD, USA), called Brain Chemistry and Genetics in Pediatric OCD, led by WSU, with collaborative partners at the University of Michigan (Ann Arbor, MI, USA) and the University of Toronto/The Hospital for Sick Children (SickKids; Toronto, ON, Canada), is focused on OCD, a severe, widespread, and chronically disabling disease. OCD affects approximately 1-3% of the population in the United States alone and approximately 50% of all OCD cases begin in childhood and adolescence.

"Initial findings at Wayne State University have shown that glutamate plays a key role in OCD,” said David Rosenberg, M.D., the Miriam L. Hamburger endowed chair of child psychiatry and professor of psychiatry in the School of Medicine at Wayne State University, and lead investigator of the project. "Glutamate is the brain's light switch, which helps turn serotonin and other chemicals off and on. Our research has shown that glutamate abnormalities in OCD have significant treatment implications. This new study will further our research by combining imaging and genetics, something never assessed in OCD patients.”

Teaming up with Dr. Rosenberg is Gregory Hanna, M.D., associate professor of psychiatry and director of the Pediatric Anxiety and Tic Disorder Program at the University of Michigan. Dr. Hanna will lead recruiting efforts for patients and their clinical characterization. In addition, Paul Arnold, M.D., Ph.D., assistant professor of psychiatry at the University of Toronto and SickKids, will lead the genetic studies. Wayne State University will lead the imaging studies at Children's Hospital of Michigan (Detroit, MI, USA).

By performing critical imaging and genetic tests of glutamate genes in 200 OCD and 200 healthy control patients, this group of scientists aims to examine glutamate changes in brain regions implicated in OCD, and to combine this information with a detailed exploration of variants within genes influencing glutamate transmission. "Brain processes visualized using magnetic resonance imaging are thought to be closer to the action of genes compared with complex behavioral phenomena like obsessive-compulsive disorder,” said Dr. Arnold. "Therefore, we hope that combining the two powerful techniques of neuroimaging and genetics will help speed up the discovery of risk genes.”

The study's findings will have considerable scientific implications as well as key ‘translational' significance in bringing research from the bench to the bedside with clinical ramifications. By combining unique clinical assessment, magnetic resonance imaging (MRI), and genetics expertise, the team of researchers will investigate biologic, genetic, and behavioral variables that may one day lead to a better understanding of pediatric OCD, which should lead to the development of new diagnostic and treatment approaches.

"This imaging/genetics project builds upon a series of genetic linkage and association studies conducted during the past 15 years,” noted Dr. Hanna. "These studies indicate genetic variants affecting the glutamate system have a primary role in the development of OCD.”

"Dr. Rosenberg is a leading international expert in pediatric OCD,” said Gloria Heppner, associate vice president for research at WSU. "His expertise in the field draws patients from all over the country and world. With his discoveries to date on glutamate and with this collaborative project focusing on combining genetics and imaging, this team of leading scientists may open new doors for patients whose brains never receive an ‘all-clear' signal.”

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