Genetic Mutation Linked to OCD-like Behavior

Neural Dysfunction Can Cause Repetitive or Obsessive Behaviors

This article was originally published in the Northwestern Now news center. 

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).

Humans and mice both have a circuit in the brain called the corticostriatal connection that regulates habitual and repetitive actions. The study found that certain synaptic receptors are important for the development of this brain circuit. When these receptors were eliminated in mice, they exhibited obsessive behavior, including over-grooming, continuously digging in their bedding and consistently failing a simple alternating-choice test in a maze.

The findings support other studies that associate receptors with human neuropsychiatric disorders, however, this is the first strong evidence that supports a biological basis for how the genes that code these receptors might affect obsessive or compulsive behaviors in humans. By demonstrating that these receptors have this role in development, scientists 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, PhD, associate professor of Physiology at Northwestern University Feinberg School of Medicine. “People with OCD are known to have abnormalities in the function of corticostriatal circuits.”

The study shed light on the importance of these receptors in the formation of the corticostriatal circuits, Contractor said.

“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 University. “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.”