Elimination of certain receptor genes led to obsessive-compulsive disorder traits
CHICAGO – A new Northwestern Medicine study found evidence suggesting how neural dysfunction in a certain region of the brain can lead to obsessive and repetitive behaviors much like obsessive-compulsive disorder (OCD).
Both in humans and in mice, there is a circuit in the brain called the corticostriatal connection that regulates habitual and repetitive actions. The study found certain synaptic receptors are important for the development of this brain circuit. If these receptors are eliminated in mice, they exhibit obsessive behavior, such as over-grooming.
The findings support other studies that associate receptors with human neuropsychiatric disorders.
This is the first strong evidence that supports the biological basis for how these genes that code for these receptors might affect obsessive or compulsive behaviors in humans. By demonstrating that these receptors have this role in development, researchers down the line will have a target to develop treatments for obsessive-compulsive behavior.
“Variations in these receptor genes are associated with human neurodevelopmental disorders, such as autism and neuropsychiatric disorders such as OCD,” said lead author Anis Contractor, associate professor of physiology at Northwestern University Feinberg School of Medicine. “People with OCD are known to have abnormalities in function of corticostriatal circuits.”
The study was published February 21 in the journal Cell Reports. The findings shed light on the importance of these receptors in the formation of the corticostriatal circuits, Contractor said.
This is the first evidence that this family of receptors impacts development of brain circuits that control repetitive behaviors.
“A number of studies have found mutations in the kainate receptor genes that are associated with OCD or other neuropsychiatric and neurodevelopmental disorders in humans,” said Contractor, who also is an associate professor of neurobiology at the Weinberg College of Arts and Sciences at Northwestern. “I believe our study, which found that a mouse with targeted mutations in these genes exhibited OCD-like behaviors, helps support the current genetic studies on neuropsychiatric and neurodevelopmental disorders in humans.”
The traits of OCD the mice in the study exhibited included over-grooming, continuously digging in their bedding and consistently failing a simple alternating-choice test in a maze.
About the study
Other Northwestern authors include Jian Xu, John Marshall, Herman Fernandes, Toshihiro Nomura, Bryan Copits, Daniele Procissi, Lei Wang, Yongling Zhu and Geoff Swanson.
The study is titled, “Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice.”
This study was funded by the following grants from the National Institutes of Health (NIH): National Institute of Mental Health grant R01MH099114; National Institute of Neurological Disorders and Stroke (NINDS) grant R21NS082785 and the McKnight Foundation (to A.C.); and NINDS grant R01NS071952 to G.T.S. J.J.M. was supported by a fellowship from NIMH grant 1F31MH099807, and J.X. was supported by NIMH grant K01MH094464.