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The serotonin hypothesis of obsessive compulsive disorder1
Abstract
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…
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“A “serotonin hypothesis” implicating the serotonin system in the pathophysiology of the disorder has been posited, arising from the therapeutic effects of the serotonin (5‐HT) reuptake inhibitors (SRIs) on OCD (Barr et al., 1993; Fineberg et al., 2012; Insel et al., 1985; for a recent study on the structure of the serotonin system using positron emission tomography [PET], see also Beliveau et al.,”
From Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction (2023) · cites this paper as Barr et al., 1993
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Stein, D. J. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09620-4 · Cited by 352
Soomro, G. M., Altman, D. G., Rajagopal, S., & Oakley Browne, M. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001765.pub3 · Cited by 342
Obsessive-compulsive symptoms in pregnancy and the puerperium:
Abramowitz, J. S., Schwartz, S. A., Moore, K. M., & Luenzmann, K. R. (2003) · Journal of Anxiety Disorders · doi:10.1016/s0887-6185(02)00206-2 · Cited by 242
Obsessive-Compulsive and Related Disorders: A Critical Review of the New Diagnostic Class
Abramowitz, J. S., & Jacoby, R. J. (2015) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032813-153713 · Cited by 185
Heterogeneity of obsessive-compulsive disorder: A literature review
Lochner, C., & Stein, D. J. (2003) · Harvard Review of Psychiatry · doi:10.1080/10673220303949 · Cited by 143
Role of dopamine in the pathophysiology and treatment of obsessive–compulsive disorder
Koo, M.-S., Kim, E.-J., Roh, D., & Kim, C.-H. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.09.148 · Cited by 125
Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction
Jalal, B., Chamberlain, S. R., & Sahakian, B. J. (2023) · Brain and Behavior · doi:10.1002/brb3.3000 · Cited by 111
“…the pathophysiology of the disorder has been posited, arising from the therapeutic effects of the serotonin (5-HT) reuptake inhibitors (SRIs) on OCD (Barr et al., 1993; Fineberg et al., 2012; Insel et al., 1985; for a recent study on the structure of the serotonin system using positron emission…”
BackgroundFonseka, T. M., Richter, M. A., & Müller, D. J. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0510-8 · Cited by 93
Metadata
- Authors
- Barr, L. C., Goodman, W. K., & Price, L. H.
- Affiliations
- Yale University (US)
- Venue
- International Clinical Psychopharmacology
- Published
- 1993-11
- Volume
- 8
- Pages
- 79-82
- ISSN
- 0268-1315 (ISSN-L)
- OpenAlex
- W2047712176
- Cited by
- 80
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 6 · 2013: 3 · 2012: 1
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Keywords
- obsessive-compulsive disorder, serotonin hypothesis, serotonergic system, serotonin reuptake inhibitors, mCPP, behavioral hypersensitivity, serotonergic dysfunction
- MeSH terms
- Animals, Arousal, Brain, Humans, Hydrocortisone, Obsessive-Compulsive Disorder, Piperazines, Prolactin, Receptors, Serotonin, Serotonin, Serotonin Receptor Agonists
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