02:39am Sunday 12 July 2020

Mice Give New Clues to Origins of OCD

Columbia Psychiatry researchers have identified what they think may be a mechanism underlying the development of compulsive behaviors. The finding suggests possible approaches to treating or preventing certain characteristics of OCD.

OCD consists of obsessions, which are recurrent intrusive thoughts, and compulsions, which are repetitive behaviors 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 behavior. By targeting this region, it may be possible to stop abnormal circuit changes before they become pathological behaviors in people at risk for obsessive-compulsive disorder (OCD). The study, which was led by Susanne Ahmari, MD, PhD, 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 centered 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 behaviors 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 behaviors 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 behaviors—in this case, repetitive grooming behavior—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 behavior 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).

The study was supported by grants from NIMH (K08MH087718; K24 MH091555), the Louis V. Gerstner, Jr. Scholars Program, the Irving Institute for Clinical and Translational Research, the Gray Matters Foundation, the Leon Levy Foundation, and a NARSAD Young Investigator Award.

The authors declare no financial or other conflicts of interest.


Columbia University Department of Psychiatry & NYS Psychiatric Institute

Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the nation and has contributed greatly to the understanding and treatment of psychiatric disorders. It is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, eating disorders, and childhood psychiatric disorders. Visit http://columbiapsychiatry.org/ for more information.

Columbia University Medical Center

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visitcumc.columbia.edu or columbiadoctors.org.

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