Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder.

Functional neuroimaging studies have advanced the understanding of the brain mediation of OCD by orbitofrontal-subcortical circuitry, but much is still unknown. Phenotypic heterogeneity could account for many of the inconsistencies among previous neuroimaging studies of OCD. Current studies are seeking to find the neurobiological basis of OCD symptom subtypes and predictors of treatment response. Future studies combining genetics and basic neuroanatomic research with neuroimaging may clarify the cause and pathophysiology of OCD. Although many lines of evidence point to dysfunction of orbitofrontal-subcortical circuitry in patients with OCD, many questions remain unanswered. Some have suggested that orbitofrontal-subcortical hyperactivity in OCD may be the result of abnormal neuroanatomic development of these structures or a failure of pruning of neuronal connections between them, as occurs in normal development, but no postmortem neuroanatomic studies of OCD exist to delineate its pathophysiology. Interventions that directly alter the indirect-direct pathway balance within frontal-subcortical circuits will allow for direct testing of the pathophysiologic hypotheses presented here. The roles of various neurochemical systems in OCD are similarly unclear. Although an abundance of indirect evidence suggests serotonergic abnormalities in patients with OCD, no direct evidence demonstrates what those abnormalities are or whether they are primary or secondary phenomena in patients with OCD. Ongoing studies of 5-HT synthesis in the brains of patients with OCD may shed light on this question.