Cerebral glutamate levels in OCD: Pathophysiology and predictors of response
Currently recruiting participants
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 who have not responded to standard therapies. However, the details of how glutamate is out of balance remains 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.
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.
Transcranial direct current stimulation
Currently recruiting participants
This study is exploring ways in which non-invasive brain stimulation can be integrated with principles of cognitive-behavioral therapy for OCD and related-disorders. More specifically, we are combining a single session of transcranial direct current stimulation (tDCS) with two sessions of a lab challenge designed to help understand exposure and response prevention (ERP). This experiment requires two appointments, scheduled 24-48 hours apart, and will take 3-4 hours to complete.
tDCS is a safe and minimally invasive form of brain stimulation that involves passing a mild electrical current (less than that of a 9 volt battery) between electrodes placed on the scalp. Some of this electrical current enters the brain and can change brain activity. ERP is gold-standard behavioral treatment for OCD that involves approaching anxiety provoking situations of a moderate level while resisting typical compulsive behaviors. This can lead to gradual reductions in anxiety and other negative emotions. While this study itself is an experiment and does not involve dedicated treatment of OCD, it may help us identify ways to improve the effect of treatment.
During the first session, participants will: complete a series of questionnaires, learn about ERP, identify moderately challenging exposures with a psychologist or psychiatrist, receive active or sham (placebo) tDCS, then complete 60 minutes of an ERP experimental challenge. Participants will then return 24-48 hours later to complete 60 additional minutes of ERP challenge. Basic physiological measures such as electroencephalography (EEG) skin conductance will be collected during most experimental procedures.
Brain Activation in OCD: A novel functional magnetic resonance imaging (fMRI) study
People with OCD respond to many things differently than people without the disorder. For example, people with OCD may be more anxious overall or may respond more to particular stimuli (such as dirt or unevenness). We are investigating the brain mechanisms underlying some of these effects using a novel functional magnetic resonance imaging (fMRI) scan sequence never before utilized in OCD. This fMRI investigation is being done in collaboration with Alan Anticevic, PhD.
Exploring the genetics of OCD
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.