Obsessive compulsive disorder: serotonin and beyond.

OCD was considered a rare, treatment refractory disorder of psychological origin, up until 20 years ago. Research in the last two decades has altered the perspectives regarding OCD. It is now clear that OCD is a prevalent disorder--about 2% of the population suffer from OCD--and that it is amenable both to psychological (cognitive-behavioural approach) and pharmacological intervention (with serotonergic medication). The biochemical and neuroanatomical (the frontal basal-thalamo cortical circuit) pathophysiology of OCD is also beginning to emerge. OCD is unique with regards to its specific response to serotonergic medication that blocks reuptake. Clomiprimine, fluoxetine, fluvoxemine, paroxetine, sertraline and citalopram were all found to be effective treatments for OCD based on large, multicentre, double-blind, placebo-controlled studies. As only serotonergic medications appear to be effective in OCD, the serotonergic hypothesis has been formulated and tested. Indeed, pharmacological challenges with specific serotonin agonists such as mCPP and sumatriptan, which were associated with transient exacerbation of OCD symptoms, are in line with the specific role of 5HT in the pathogenesis of OCD. However, this serotonergic hypothesis, while necessary, is not sufficient. It is clear that the dopaminergic and autoimmune mechanism are also implicated in the pathogenesis of OCD. Further studies are required to understand the relevance of the serotonergic and non-serotonergic systems in OCD, and to highlight the various possible subtypes of this intriguing disorder.