Obsessive-Compulsive Disorder (OCD) is a not uncommon, chronic, debilitating condition for which few effective treatments exist. While neuropsychiatric abnormalities have long been noted, of the disorder are poorly understood. Recently spurred by findings of therapeutic efficacy of potent serotonin (5HT) reuptake blockers, a 5HT dysregulation theory has been proposed. Limitations of existing findings and theories for OCD include: 1) only small samples have been studied; 2) inconsistent biochemical and neuropsychiatric findings across studies; 3) no attempts to integrate biochemical and neuropsychiatric findings; 4) only a subset (50%) of OCD patients respond to 5HT reuptake blockers, suggesting pathophysiological heterogeneity; 5) where 5HT abnormalities are found, they are almost aways in the direction of increased, not decreased, 5HT activity and sensitivity; 6) the high baseline 5HT subgroup appears to be the subgroup responsive to chronic 5HT reuptake blocker therapy. This proposal will e 70 OCD patients, 35 normal controls and 35 anxiety disorder (Social Phobic) controls on a number of serotonergic (behavioral and neuroendocrine responses to the selective 5HT agonist M-UP), neuropsychiatric (neurological soft signs) and neuropsychological measures. The neuropsychological battery specifically explores frontal lobe and septohippocampal dysfunction in OCD. Data will be analyzed to see if serotonergic, neuropsychiatric and/or neuropsychological abnormalities in OCD can be identified; how neuropsychiatric and biochemical findings correlate; how neuropsychological abnormalities cluster with these findings. Overall, the studies should delineate whether pathophysiologically distinct (biochemically and neurologically impaired) subgroups of OCD patients exist. They should also help to clarify the biochemical and neuropsychiatric contributions to aberrant neuropsychological functioning in OCD. Future studies will address how these baseline markers correlate with treatment outcome, and how they are affected by treatment.
