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A team of scientists from across the country will use a $15.6 million award from the National Institute of Mental Health to investigate the brain networks central to obsessive compulsive disorder (OCD). The work will build on more than 15 years of research by lead investigator Suzanne N. Haber, Ph.D. and collaborators to understand the underlying biology of the disease and guide the development of effective treatments.

“Obsessive compulsive disorder is among the most disabling psychiatric disorders,” said Haber, professor of Pharmacology and Physiology, Neuroscience and Psychiatry at the University of Rochester School of Medicine and Dentistry. “It affects one to three percent of the population worldwide, yet it hasn’t received the same level of attention as other mental health disorders. We’re excited to receive this funding and use translational methods to understand circuit dysfunction in the disease and to develop new treatment approaches that can improve the lives of patients.”

The five-year grant funds a Silvio O. Conte Center for Basic and Translational Mental Health Research at the University of Rochester. Haber has received previous Conte Center grants that have propelled scientists’ understanding of the disease. Major findings include the discovery of a narrower, more defined network of brain regions that underlie the disorder. Dubbed the ‘OCD network,’ the new grant will allow scientists to test the idea that behavioral inflexibility in OCD results from faulty connections between brain circuits in this network.  

“The identification of the OCD network is the result of years of research by us and others that demonstrates a set of connected brain structures that are central to linking stimuli to decisions that we make about actions that lead to certain outcomes,” noted Haber.

Individuals with OCD often compulsively avoid or take specific actions to avoid a potential bad outcome, despite a low likelihood of that outcome occurring. For example, a person may wash their hands constantly because they want to avoid contamination. This action persists despite the awareness that it is not productive. “By studying this network and its role in different aspects of decision making and behavioral flexibility we hope to better understand how dysfunction of neural connections can result in obsessions and compulsions,” noted Haber.  

The research team will focus on:

• Understanding the connections and complex brain circuit interactions in the OCD network that are linked to persistent avoidance behavior.
• Identifying abnormalities within the connections that are associated with impairments in behavioral flexibility, resulting in persistent avoidance in individuals with OCD.
• Studying the effects of modulation on those circuits and on the behavioral inflexibility in OCD.

The University of Rochester team will combine studies of anatomy with high-resolution diffusion and functional imaging to identify relevant connections in the OCD network. These data will help scientists probe abnormalities using imaging tools in people with OCD. It will also help identify individual variation in critical network locations. Finally, these results will be used to explore new ways to modulate the network, such as through the use of deep brain stimulation and low-intensity focused ultrasound.

Haber notes that the OCD network, which regulates normal behaviors related to the flexibility of responses, is central not only to OCD, but a wide range of other mental health conditions, such as depression, post-traumatic stress disorder (PTSD) and addiction. Findings from this work could influence the management of these illnesses, as well.

In addition to the University of Rochester, six other institutions are participating in the research:

• Brown University
• McLean Hospital, Harvard University
• Massachusetts General Hospital, Harvard University
• Rhode Island Hospital
• University of Pittsburgh
• Washington University

Conte Centers are named after a former congressman from Massachusetts who championed neuroscience research and the care of the severely mentally ill. They are designed to bring scientists with diverse but complimentary backgrounds together to improve the diagnosis and treatment of mental health disorders. There are 15 Conte Centers in the U.S.