Positron emission tomography (PET) studies in patients with obsessive- compulsive disorder (OCD) have yielded conflicting results. Most studies to date have used a radiopharmaceutical with a relatively long half-life (18FDG) and compared small numbers of OCD patients to normal controls or patients with other diagnoses such as major depression. Intraindividual differences in obsessional state may account for at least part of the variation from study to study. For example, whether or not a patient is having obsessional thoughts or is concerned with being contaminated while undergoing the scan might profoundly alter the PET findings over short periods of time (i.e., minutes). To determine how patients' obsessional state influences the PET scan over short periods of time, we are proposing to study 32 OCD patients by means of a short half-life radiopharmaceutical tracer, 15-O-labeled CO2, that will allow the investigators to perform multiple scans on the same patient and permit a research design in which each patient can be tested with only a 10 minute interval between a """"""""resting"""""""" state and a stimulated """"""""provoked"""""""" (i.e., """"""""obsessing"""""""") state. Patients will thus serve as their own controls. 15-O-CO2 will be used instead of 18FDG so that scans can be repeated in each patient with only a brief interval between scans. To help assess the effect of pharmacologic treatment, and in an effort to determine predictors of treatment response, OCD subjects will undergo an identical PET protocol after three months of open treatment with a serotonergic reuptake inhibitor. In addition, a cohort of 10 normal subjects, matched to a subset of the OCD patients with respect to age, gender, and stimuli, will be studied using the identical paradigm to serve as a control group.
