The serotonin hypothesis of obsessive compulsive disorder

Int Clin Psychopharmacol. 1993 Nov;8 Suppl 2:79-82. doi: 10.1097/00004850-199311002-00011.


The above studies investigating the responsivity of the 5-HT system to provocation provide some support for the hypothesis drawn from the results of pharmacologic treatment trials and studies of biological markers that dysregulation of the 5-HT system may be involved in the pathogenesis of OC symptoms. While results of several studies document blunting of neuroendocrine responses to 5-HT agonists, only one study suggests a small increase in responsiveness compared to healthy controls. Combined with neurophysiologic data suggesting net increases in 5-HT functioning following treatment with SRIs, these results suggest that the primary deficit in OCD is not one of increased 5-HT responsivity. Exacerbation of OC symptoms sometimes observed during mCPP challenge is not entirely consistent with this hypothesis and additional studies are required to clarify the significance of these findings. However, behavioral hypersensitivity coupled with neuroendocrine hyposensitivity to serotonergic stimulation might characterize the serotonergic dysfunction accompanying OCD. The complexity of the 5-HT system, and the likelihood that behavioral and neuroendocrine responses are mediated by different receptor subtypes makes this hypothesis entirely plausible. The efficacy of SRIs in the treatment of OCD remains the firmest evidence of serotonergic involvement in this condition. Results of challenge studies in OCD also suggest a possible dysregulation in 5-HT function, although the precise nature of this disturbance remains elusive. Neuroendocrine responses to 5-HT agonists generally are consistent with a tendency toward hyposensitivity in OCD. Behavioral results, while more mixed, indicate a hypersensitivity to 5-HT agonists. Further refinement in dependent and independent variables used in challenge studies may clarify remaining questions.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Arousal / drug effects
  • Arousal / physiology
  • Brain / drug effects
  • Brain / physiopathology
  • Humans
  • Hydrocortisone / blood
  • Obsessive-Compulsive Disorder / drug therapy
  • Obsessive-Compulsive Disorder / physiopathology*
  • Obsessive-Compulsive Disorder / psychology
  • Piperazines
  • Prolactin / blood
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin / physiology*
  • Serotonin Receptor Agonists


  • Piperazines
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin
  • Prolactin
  • 1-(3-chlorophenyl)piperazine
  • Hydrocortisone