Different roles for serotonin in anti-obsessional drug action and the pathophysiology of obsessive-compulsive disorder

Background: There is a major role for serotonin in the mechanism of anti-obsessional drug action. Drugs that block uptake of noradrenaline are not effective in the treatment of obsessive- compulsive disorder (OCD), while drugs that potently bock serotonin reuptake are effective. While enhancement of serotonin neurotransmission is clearly involved in the treatment of OCD, the role of serotonin in the pathophysiology of OCD is less clear. Method: This paper provides a brief, focused review of the literature regarding treatment of OCD, the effects of drugs with selective action at various serotonin receptors and results of neurotransmitter depletion studies in patients with OCD. Results: Some patients with OCD may experience remission of OCD symptoms during intoxication with psychedelic drugs that have potent 5-HT(2A/2C) agonist activity. These findings, coupled with results from serotonin depletion studies in depressed and OCD patients, suggest that enhancement of serotonin neurotransmission may underlie both antidepressant and anti-obsessional drug action, although the targeted brain areas may differ. Conclusions: OCD may not involve a dysfunction of the serotonin system. Rather, it is more likely to involve a dysfunction of specific brain circuits, particularly in the frontal cortex. Modulation of these circuits by serotonin neurons may underlie the specific action of anti-obsessional drugs.