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The serotonin hypothesis of obsessive compulsive disorder
L C Barr1, W K Goodman, L H Price
1Department of Psychiatry, Yale University, New Haven, CT 06519.
International Clinical Psychopharmacology
|November 1, 1993
Summary
Obsessive-compulsive disorder (OCD) may involve serotonin (5-HT) system dysregulation. While selective serotonin reuptake inhibitors (SRIs) are effective, challenge studies show mixed results, suggesting hypersensitivity in behavior and hyposensitivity in neuroendocrine responses.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Dysregulation of the serotonin (5-HT) system is hypothesized to be involved in the pathogenesis of obsessive-compulsive (OC) symptoms.
- Pharmacological treatment trials and biological marker studies suggest a role for 5-HT in OCD.
- Selective serotonin reuptake inhibitors (SRIs) are effective in treating OCD, providing strong evidence for serotonergic involvement.
Purpose of the Study:
- To investigate the responsivity of the 5-HT system to provocation in individuals with OCD.
- To clarify the nature of serotonergic dysfunction in the pathogenesis of OCD.
- To reconcile conflicting findings from pharmacological and challenge studies regarding 5-HT system function in OCD.
Main Methods:
- Review of studies investigating 5-HT system responsivity to provocation, including neuroendocrine and neurophysiological challenge studies.
- Analysis of results from pharmacological treatment trials and studies of biological markers in OCD.
- Comparison of behavioral and neuroendocrine responses to 5-HT agonists between individuals with OCD and healthy controls.
Main Results:
- Neuroendocrine responses to 5-HT agonists generally suggest a tendency toward hyposensitivity in OCD.
- Behavioral responses to 5-HT agonists in OCD are mixed, with some studies indicating hypersensitivity.
- Exacerbation of OC symptoms during mCPP challenge is inconsistent with a primary deficit of increased 5-HT responsivity.
Conclusions:
- The primary deficit in OCD is unlikely to be increased 5-HT responsivity, considering SRI efficacy and challenge study results.
- A plausible hypothesis for serotonergic dysfunction in OCD involves behavioral hypersensitivity coupled with neuroendocrine hyposensitivity to serotonergic stimulation.
- Further refinement of challenge study methodologies is needed to fully elucidate the complex role of the 5-HT system in OCD pathogenesis.