Hostname: page-component-76d6cb85b7-pn7tm Total loading time: 0 Render date: 2026-07-15T17:50:23.542Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  06 August 2018

Pedro L. Delgado  and
Fransisco A. Moreno
Pedro L. Delgado*
Affiliation:
Department of Psychiatry, University of Arizona College of Medicine, 7402 AHSC, 1501 N. Campbell, Tucson, Arizona 85274, USA
Fransisco A. Moreno
Affiliation:
Department of Psychiatry, University of Arizona College of Medicine, 7402 AHSC, 1501 N. Campbell, Tucson, Arizona 85274, USA
*
Correspondence: Dr P. L. Delgado, Department of Psychiatry, University of Arizona College of Medicine, 7402 AHSC, 1501 N. Campbell, Tucson, Arizona 85274, USA. Fax: +1 520 626 6050; e-mail: delgado@u.arizona.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

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 ofthe 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-HT2A/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 ofthe 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.

Information

Type
Research Article
Information
The British Journal of Psychiatry , Volume 173 , Issue S35: New perspectives in research and treatment of obsessive-compulsive disorder , August 1998 , pp. 21 - 25
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Baxter, L. R. (1991) PET studies of cerebral function in major depression and obsessive-compulsive disorder: the emerging prefrontal cortex consensus. Annals of Clinical Psychiatry, 3, 103–109.Google Scholar
Baxter, L. R., Schwartz, J. M., Bergman, K. S., et al (1992) Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Archives of General Psychiatry, 49, 681–689.Google Scholar
Blier, P. & de Montigny, C. (1994) Current advances in the treatment of depression. Trends in the Pharmacological Sciences, 15, 220–226.Google Scholar
Barr, L. C., Goodman, W. K. & Lawrence, H. (1993) The serotonin hypothesis of obsessive-compulsive disorder. International Clinical Psychopharmacology, 8 (suppl. 2), 79–82.Google Scholar
Barr, L. C., Goodman, W. K., McDougle, C. J., et al (1994) Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors. Archives of General Psychiatry, 51, 309–317.Google Scholar
Bloom, F. E. (1995) Introduction to preclinical neuropsychopharmacology. In Psychopharmacology: The Fourth Generation of Progress (eds Bloom, E. & Kupfer, D. J.), pp. 1–7. New York: Raven Press.Google Scholar
Delgado, P. L., Charney, D. S., Price, L. H., et al (1990) Serotonin function and the mechanism of antidepressant action: Reversal of antidepressant induced remission by rapid depletion of plasma tryptophan. Archives of General Psychiatry, 47, 411–418.CrossRefGoogle ScholarPubMed
Delgado, P. L., Price, L. H., Miller, H. M., et al (1991) Rapid serotonin depletion as a provocative challenge test for patients with major depression: Relevance to antidepressant action and the neurobiology of depression. Psychopharmacology Bulletin, 27, 321–330.Google Scholar
Delgado, P. L. Price, L. H., Hetlinger, G. R., et al (1992) Neurochemistry of affective disorders. In Handbook of Affective Disorders, Second Edition (ed. Paykel, E. S.), pp. 219–253. Edinburgh: Churchill Livingstone.Google Scholar
Delgado, P. L., Miller, H. M., Salomon, R. M., et al (1993) Monoamines and the mechanism of antidepressant action; effects of catecholamine depletion on mood in patients treated with antidepressants. Psychopharmacology Bulletin, 29, 389–396.Google ScholarPubMed
Erzegovesi, S., Ronchi, P. & Smeraldi, E. (1992) 5-HT receptor and fluvoxamine effect in obsessive-compulsive disorder. Human Psychopharmacology, 7, 287–289.CrossRefGoogle Scholar
Goodman, W. K., Price, L. H., Rasmussen, S. A., et al (1989) The Yale-Brown obsessive-compulsive scale: II. Validity. Archives of General Psychiatry, 43, 451–456.Google Scholar
Goodman, W. K., Price, L. H., Delgado, P. L., et al (1990) Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: comparison of fluvoxamine and desipramine. Archives of General Psychiatry, 47, 577–585.CrossRefGoogle ScholarPubMed
Goodman, W. K., Kozak, M. J., Liebowitz, M., et al (1996) Treatment of obsessive-compulsive disorder with fluvoxamine: a multicenter, double-blind, placebo-controlled trial. International Clinical Psychopharmacology, 11, 21–29.CrossRefGoogle Scholar
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology Revised DHEW Pub. (ADM). Rockville, MD: National Institute for Mental Health.Google Scholar
Hanes, K. R. (1996) Serotonin, psilocybin and body dysmorphic disorder: a case report. Journal of Clinical Psychopharmacology, 16, 188–189.CrossRefGoogle ScholarPubMed
Henrietta, L. L. & Rapoport, J. L. (1987) Relief of obsessive-compulsive symptoms by LSD and psilocybin. American Journal of Psychiatry, 144, 1239–1240.Google Scholar
Hollander, E., DeCaria, C. M., Nitescu, A., et al (1992) Serotonergic function in obsessive-compulsive disorder: behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers. Archives of General Psychiatry, 49, 21–28.Google Scholar
Lam, R. W., Zis, A. P., Grewal, A., et al (1995) Effects of acute tryptophan depletion in seasonal affective disorder in remission with light therapy. Archives of General Psychiatry, 53, 41–44.Google Scholar
Mayberg, H. S. (1994) Frontal lobe dysfunction in secondary depression. Special Issue. The frontal lobes and neuropsychiatric illness. Journal of Neuropsychiatry and Clinical Neuroscience, 6, 428–442.Google Scholar
Mazure, C. M., Nelson, J. C. & Price, L. H. (1986) Reliability and validity of symptoms of major depressive illness. Archives of General Psychiatry, 43, 451–456.CrossRefGoogle ScholarPubMed
Miller, H. L., Delgado, P. L., Salomon, R. M., et al (1996a) Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Archives of General Psychiatry, 53, 117–128.Google Scholar
Miller, H. L., Delgado, P. L., Salomon, R. M., et al (1996b) Effects of alpha-methyl-para-tyrosine (AMPT) in drug-free depressed patients. Neuropsychopharmacology, 14, 151–158.CrossRefGoogle ScholarPubMed
Moreno, F. A. & Delgado, P. L. (1997) Hallucinogen induced relief of obsessions and compulsions. American Journal Psychiatry, 154, 1037–1038.Google Scholar
Moreno, F. A., McKnight, K., Gelenberg, A. J., et al (1998) Tryptophan deletion and vulnerability to depression. Biological Psychiatry, in press.Google Scholar
Murphy, D. L., Pickar, D. & Atterman, I. S. (1982) Methods for the quantitative assessment of depressive and manic behavior. In The Behavior of Psychiatric Patients (eds Burdock, E. I., Sudilovsky, A. & Gershon, S.), pp. 355–392. New York: Marcel Dekker.Google Scholar
Price, L. H., Goddard, A. W., Barr, L. C., et al (1995) Pharmacological challenges in anxiety disorders. In Psychopharmacology: The Fourth Generation of Progress (4th edn) (eds Bloom, F. E. & Kupfer, D. J.), pp. 1311–1323. New York: Raven Press.Google Scholar
Satel, S. L., Krystal, J., Delgado, P. L., et al (1995) Serotonin mediation of cue-induced cocaine craving: Rapid tryptophan depletion attenuates desire for cocaine. American Journal of Psychiatry, 152, 778–783.Google Scholar
Smith, K. A., Fairburn, C. G. & Cowen, P. J. (1997) Relapse of depression after rapid depletion of tryptophan. Lancet, 349, 915–919.CrossRefGoogle ScholarPubMed
Young, S. N., Smith, S. E., Pihl, R., et al (1985) Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology, 87, 173–177.CrossRefGoogle ScholarPubMed

This journal is not currently accepting new eletters.

eLetters

No eLetters have been published for this article.