Wayne State University School of Medicine researchers recently discovered that the chemical glutamate plays a major role in children with obsessive-compulsive disorder.
David Rosenberg, M.D., the Miriam L. Hamburger Endowed Chair of Child Psychiatry and professor of Psychiatry in the School of Medicine, collaborated with researchers at the University of Michigan, Children's Hospital of Michigan and University of Toronto/ Hospital for Sick Kids. This international team discovered that the chemical glutamate plays a key role in children with OCD.
OCD is a debilitating neuropsychiatric condition that affects approximately 1 percent to 3 percent of the population worldwide. As many as 80 percent of all OCD cases begin in childhood and adolescence. In Dr. Rosenberg's study, children with OCD had abnormal glutamate levels in key brain regions that were reversible with effective treatment.
"Since our initial findings at Wayne State University, basic neuroscience, genetic, brain imaging and novel treatment development studies all converged to show that glutamate has a key role in OCD," Dr. Rosenberg said. "If we think of serotonin as analogous to light that lets us see in the dark, glutamate is the brain's light switch or brain modulator which helps turn serotonin and other chemicals off and on."
Wayne State's researchers, along with Gregory Hanna, M.D., of the University of Michigan and researchers at the University of Toronto/Hospital for Sick Kids in Toronto, Ontario, have a longstanding collaboration and recently published the first OCD study combining brain imaging and genetics studies in the same children with OCD in the March 2009 issue of the journal Brain Imaging and Behavior. All brain images and blood samples were collected at Wayne State with blood samples genetically analyzed in Drs. James Kennedy and Paul Arnold's laboratory at the University of Toronto and Hospital for Sick Kids.
The studies found significant associations between glutamate receptor and transporter genes and abnormal brain volumes in brain regions implicated in OCD such as the thalamus ("grand central station" in the brain), caudate nucleus (the brain's "secretary"), anterior cingulate cortex (the brain's arousal center) and orbital prefrontal cortex (the brain's "executive decision maker").
This work showing glutamate abnormalities in OCD has significant treatment implications. Based in part on initial findings at the School of Medicine showing glutamate abnormalities in OCD, new treatment approaches using glutamate modulator drugs such as riluzole, which is used for treating Lou Gehring's disease, and others have been used in adults and children with OCD. Initial studies have shown great promise, and studies using riluzole are being conducted by the National Institute of Mental Health in children with OCD. The trial is ongoing and results are unavailable.
"This study at NIMH demonstrates how work first done at Wayne State University not only has scientific implications but has key translational relevance in bringing work from the bench to the bedside with potential clinical ramifications," Dr. Rosenberg said. Wayne State University, the University of Michigan and the University of Toronto/Hospital for Sick Kids in Toronto have recently submitted a Collaborative R01 grant to NIMH that is being considered for funding. Wayne State University is the lead site and coordinating center on this application.
A second paper was recently published online and will be available in the May issue of Psychiatry Research: Neuroimaging by the same team of researchers. This paper continues the team's study of pediatric OCD patients and is the first published report examining the relationship between genetic variation and a neurochemical phenotype in OCD. This study found that there is a significant association between variation in a key glutamate receptor gene and glutamate levels in the brain's arousal center, the anterior cingulate cortex. No association was found between genetic markers and brain imaging measures in brain regions not implicated in the pathology of OCD.
Along with Dr. Rosenberg, collaborators on the projects include Frank P. MacMaster, Ph.D., Yousha Mirza, M.D., Phillip Easter, research assistant, and Michelle Rose, research assistant, of Wayne State University and The Children's Hospital of Michigan; Gregory Hanna, M.D., University of Michigan; Paul Daniel Arnold, M.D., Hospital of Sick Kids and the University of Toronto; and Margaret A. Richter, M.D.,Tricia Sicard, research assistant, Eliza Burroughs, research assistant, and James Kennedy, M.D.,University of Toronto.