Current Non-Treatment Studies

Cerebral glutamate levels in OCD: Pathophysiology and predictors of response

HIC: 0803003626

A number of studies using different techniques have suggested that the neurotransmitter glutamate is present at excessive levels in at least some patients with OCD. This idea has motivated our use of glutamate-modulating drugs in OCD that has not responded to standard therapies. However, the details of how glutamate is out of balance in OCD remain unclear. Likewise, it is unclear whether glutamate dysregulation contributes to all forms of OCD or only to some subtypes. Better understanding this issue may, in the future, help us select which therapies are most likely to work for individual patients.

We use an imaging method, magnetic resonance spectroscopy (MRS), that allows us to measure the levels of glutamate and related molecules in the brain. This is done in a brain scanner very similar to that used for the MRI imaging that is standard in all hospitals. By better understanding how and where glutamate is disrupted in OCD, we hope to expand our knowledge of the biological changes that contribute to the disorder and how to develop new medication strategies to address them.

Participation in this study involves answering questions about your psychiatric condition and then having a single MRS scan. An MRS scan is very similar to an MRI scan, which is done routinely in clinical care; it requires you to lie still in a large scanner for about 90 minutes. Some people with claustrophobia find this difficult, as the scanner is rather confined. Both OCD patients who are on no medications and those who are on medications and are entering one of our treatment studies are eligible for this study.

Our MRS investigations are done in collaboration with Graeme Mason, Ph.D., at the Yale Magnetic Resonance Research Center. These studies are supported by grants from the Doris Duke Charitable Foundation and from the National Institutes of Health, through a YCCI scholar award from the Yale Center for Clinical Investigation.

Brain activation during cognitive control in OCD: A functional magnetic resonance imaging study

HIC: 0803003626

People with OCD respond differently to many things than people without the disorder; for example, they may be more anxious overall, may respond more to particular stimuli (such as dirt), may react more when they make a mistake, and may suffer from indecision or doubt. We are investigating the brain mechanisms underlying some of these effects, using functional magnetic resonance imaging (fMRI).

Participation in this study involves answering questions about your psychiatric condition and then having a single 90-minute fMRI scan. An fMRI scan is very similar to a regular MRI scan, which is done routinely in clinical care; it requires you to lie still in a large scanner for about 90 minutes. During this time you will watch shapes and images on a screen and be asked to push a button in response to certain events. The scanner will monitor your brain’s response to these images and actions.

This fMRI investigation is being done in collaboration with Chiang-Shan (Ray) Li, MD. It is supported by a grant from the National Institutes of Health.

Sensory gating and learning in OCD

HIC: 0803003626

People with OCD and related conditions sometimes have difficulty screening out lights, sounds, touches, and events that other people would ignore. We are examining this phenomenon, and related sensory processing phenomena in OCD. We hope that better understanding of sensory processing, attention, and related phenomena in OCD will lead to better understanding of the underlying neurobiology, ultimately leading to new approaches to diagnosis and treatment.

Participation in this study involves a 2-hour (or so) session, in which participants perform a variety of simple tasks (watching a computer monitor, pushing buttons in response to specific stimuli). For some tests, electrical monitoring of brain activity using an electroencephalogram cap, or of muscle responses using wires taped to the skin, give us additional information about how the brain responds during these tasks.

This investigation is being done in collaboration with Linda Mayes, MD, and Michael Crowley, PhD, in the Yale Developmental Electrophysiology Laboratory at the Yale Child Study Center.

Exploring the genetics of OCD

HIC # 0803003626

It is clear that the risk for developing OCD depends in part on our genes; but the specific genes that contribute to OCD, and how they do so, are not well understood. Patients who we see in our clinic have the opportunity to give blood for genetic analysis. By comparing the specific genes of patients with OCD with other patients or with individuals with no psychiatric diagnosis, we hope to better understand the various complicated factors that contribute to the genetics of the illness.

A long-term outcome study in OCD: Symptom stability and predictors of response

HIC #0605001476

OCD is often a lifelong condition. How do symptoms change over time? What patient characteristics, lab tests, or clinical characteristics can help us predict who will respond to which treatments, and how patients’ symptoms will develop over time?

To address these symptoms, we are investigating the long-term clinical course of patients treated in our clinic in the 1980s and 1990s. By following up with these patients 10-20 years later, we can learn valuable information about how OCD develops and responds to treatment over years.