Neurobiology of obsessive compulsive disorder: a possible role for serotonin.
At the current time, it appears that the only medications with consistent antiobsessional effects are the potent serotonin uptake blockers (clomipramine, fluoxetine, and fluvoxamine). Not only is serotonin uptake blockade an apparent prerequisite for clinical improvement, but there is a correlation between the magnitude of clinical response and the reduction in various serotonin markers during treatment with these drugs. Further evidence for the importance of serotonin in pharmacologic mediation of antiobsessional effects comes from a recent study in which administration of a serotonin antagonist (metergoline) to obsessive compulsive disorder (OCD) patients partly reversed the clinical improvement observed with clomipramine treatment. Although these observations have implicated serotonin in the mechanism of antiobsessional drug action, there is still little evidence demonstrating a role for serotonin in the pathophysiology of OCD. This review summarizes various studies of serotonin function in untreated OCD patients and concludes that the most compelling evidence for an abnormality has come from single-dose challenge studies of serotonin receptor agonists in untreated OCD patients. These studies remain controversial, but a preliminary interpretation of the results suggests that OCD patients may be more sensitive than healthy controls to the behavioral effects of one such serotonin agonist, m-CPP. An abnormality in the sensitivity to endogenous serotonin may link OCD research to the broader scientific question of serotonin's role in the modulation of aggression.
Winslow
J T
JT
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md.
Insel
T R
TR
D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology*
D010879:Piperazines; D011985:Receptors, Serotonin; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine