2 min readMice Give New Clues to Origins of OCD

New York, NY – Columbia Psychiatry researchers have identified what they think may be a mechanism underlying the development of compulsive behaviours. The finding suggests possible approaches to treating or preventing certain characteristics of OCD. [Video]

OCD consists of obsessions, which are recurrent intrusive thoughts, and compulsions, which are repetitive behaviours that patients perform to reduce the severe anxiety associated with the obsessions. The disorder affects 2–3 percent of people worldwide and is an important cause of illness-related disability, according to the World Health Organization.

Using a new technology in a mouse model, the researchers found that repeated stimulation of specific circuits linking the brain’s cortex and striatum produces progressive repetitive behaviour. By targeting this region, it may be possible to stop abnormal circuit changes before they become pathological behaviours in people at risk for obsessive-compulsive disorder (OCD). The study, which was led by Dr. Susanne Ahmari, assistant professor of clinical psychiatry at Columbia Psychiatry and the New York State Psychiatric Institute, was published in the June 7 issue of Science.

While the obsessions and compulsions that are the hallmarks of OCD are thought to be centred in the cortex, which controls thoughts, and the striatum, which controls movements, little is known about how abnormalities in these brain regions lead to compulsive behaviours in patients.

To simulate the increased activity that takes place in the brains of OCD patients, Dr. Ahmari and her colleagues used a new technology called optogenetics, in which light-activated ion channels are expressed in subsets of neurons in mice, and neural circuits are then selectively activated using light delivered through fiberoptic probes.

“What we found was really surprising,” said Dr. Ahmari. “That activation of cortico-striatal circuits did not lead directly to repetitive behaviours in the mice. But if we repeatedly stimulated for multiple days in a row for only five minutes a day, we saw a progressive development of repetitive behaviours―in this case, repetitive grooming behaviour―that persisted up to two weeks after the stimulation was stopped.”

She added, “And not only that, when we treated the mice with fluoxetine, one of the most common medications used for OCD, their behaviour went back to normal.” The current study, as well as others currently being performed by Dr. Ahmari and her team, may ultimately provide clues for new treatment targets in terms of both novel drug development and direct stimulation techniques, including deep brain stimulation (DBS).

Publication: Repeated Cortico-Striatal Stimulation Generates Persistent OCD-Like Behavior. Susanne E. Ahmari, Timothy Spellman, Neria L. Douglass, Mazen A. Kheirbek, H. Blair Simpson, Karl Deisseroth, Joshua A. Gordon, and René Hen.  Science (June 2013): http://www.sciencemag.org/citmgr?gca=sci;340/6137/1234

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