The neurobiology of obsessive-compulsive disorder : neuroanatomy, neurochemistry, and pharmacotherapy

[摘要] ENGLISH ABSTRACT:Obsessive-compulsive disorder (OCD) is characterized by intrusivethoughts (obsessions) and repetiti ve mental acts or behaviours(compulsions) . For many years, it was considered a ratheruncommon condition, caused by unconscious conflict, and somewhatresistant to treatment. In recent decades, however, it hasemerged that OCD is a highly prevalent disorder, mediated byparticular neuroanatomical circuits (e.g. striatal pathways) andneurochemical systems (e.g. the serotonin system), and responsiveto treatment with serotonin reuptake inhibitors (SRIs) .Nevertheless, many questions remain; about the specificity ofneuroanatomical findings to OCD, about the role of the multipleserotonin (5-HT) receptor subtypes (e.g. 5-HT10)' and about theappropriate pharmacotherapy for patients resistent to SRItreatment? In a series of studies, 1) the neuroanatomy of OCD wasassessed by means of magnetic resonance imaging andneuropsychological testing, 2) the neurochemistry of OCD wasassessed by means of functional brain imaging after administrationof a 5-HT10 agonist, and 3) the pharmacotherapy of OCD wasexplored in a series of treatment-refractory OCD and OCD spectrumdisorder patients using SRI augmentation with a dopamine blocker.Although no significant difference was found in the volume of thecaudate in women with OCD and controls, there was a significantcorrelation between caudate volume and neuropsychologicaldysfunction in patients, consistent with evidence of striatalinvolvement in OCD. Functional imaging demonstrated behaviouralheterogeneity, but brain-behaviour correlations were positive,consistent with preclinical evidence of a role for the 5-HTlDreceptor in the mediation of OCD. Finally, preliminary treatmentfindings with dopamine blocker augmentation of a SRI werepromising, consistent with preclinical understandings of theinteractions between the dopamine and serotonin systems. Although oeD is a complex disorder, a number of future research avenueshold promise for providing a thorough delineation of itspathogenesis.

[发布机构] Stellenbosch University