A Magnetic Resonance Spectroscopic Examination of Children and Adolescents Taking Riluzole for Obsessive-Compulsive Disorder

Overview

Background: * Obsessive-compulsive disorder (OCD) is a common childhood disorder that often does not respond to standard treatments. Researchers are exploring the role that a brain chemical called glutamate plays in symptoms of OCD, and are testing a drug called riluzole that reduces glutamate to see if changing the levels of glutamate in the brain will help treat the disorder. * Researchers are interested in using magnetic resonance spectroscopy (MRS), a type of magnetic imaging, to take pictures of various chemicals in the brain. MRS images will be used to detect changes in brain levels of glutamate in children taking riluzole. Objectives: \- To use magnetic resonance spectroscopy to study the levels of glutamate in the brains of children and adolescents who have been taking riluzole. Eligibility: \- Children and adolescents ages 7 to 17 who are enrolled in the current NIMH riluzole trial protocol (05-M-0225), who are able to lie still in the scanner for about an hour each time, and who are willing to have up to three MRS scans. Design: * Researchers will study some children/adolescents before they begin to take the study medication riluzole or placebo these children will have an MRS scan before starting the study medication. The scan will take about an hour. * About 2 weeks after reaching the full dose on the study medication, participants will have a second hour-long MRS scan. Participants will have a third MRS scan after being on the study medication for 12 weeks. * Some children who have already completed 12 weeks on riluzole or placebo, and are now taking riluzole, will have only one MRS scan.

Objective This study uses magnetic resonance spectroscopy (MRS) to measure the neurotransmitter glutamate in the anterior cingulate cortex (and, if tolerated, the left caudate nucleus and possibly the thalamus) in children and adolescents. Study Population All of the subjects will be participants in an ongoing double-blind placebo-controlled trial (05-M-0225) of a glutamate antagonist, the drug riluzole, for Obsessive-Compulsive Disorder (OCD). The subjects are male and female children and adolescents, ages 7-17 years. They will all have met criteria for clinically significant OCD and will have failed to benefit from standard-of-care treatments or have been unable to tolerate the treatments. Some of the subjects will also have a diagnosis on the autism spectrum. Design In one group of sixteen young people, glutamate will be measured in the anterior cingulate cortex at three points in time: * at baseline, before starting riluzole or placebo; * within ten to fourteen days of the baseline evaluation, after reaching full dose of the study drug (active drug or placebo) to which the sixteen subjects have just been randomized; * at the end of the twelve weeks of the double-blind phase of the study. In a second group of sixteen young people, all of whom are subjects in the open-label phase of the same study, glutamate will be measured (first) in the anterior cingulate cortex at a single point in time when each subject has achieved steady state on the open-label drug riluzole. If the subject tolerates additional time in the scanner, glutamate will also be measured in the left caudate and possibly in the left thalamus. Glutamate levels in this group will be correlated with change in OCD measures. Outcome Measures * In the first group, change in glutamate activity in anterior cingulate associated with active drug (riluzole) administration, as compared with change in glutamate activity for the subjects taking placebo. * In the second group, correlation between serum riluzole level, glutamate activity (or flux) in anterior cingulate (and possibly in the caudate and thalamus), and therapeutic effect.