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Role of serotonin in obsessive-compulsive disorder

Published online by Cambridge University Press:  06 August 2018

H. G. Baumgarten  and
Z. Grozdanovic
H. G. Baumgarten*
Affiliation:
Institute of Anatomy, University Clinic Benjamin Franklin, Free University of Berlin, Germany References: Baumgarten & Grozdanovic, 1995, 1997; Jacobs & Fornai, 1993; Unnoila et al, 1993; Soubrie, 1986; Spoont, 1992; Sugihara et al, 1995; Törk 1990; van de Kar & Brownfield, 1993
Z. Grozdanovic
Affiliation:
Institute of Anatomy, University Clinic Benjamin Franklin, Free University of Berlin, Germany
*
Correspondence: Professor H. G. Baumgarten, Institute of Anatomy, University Clinic Benjamin Franklin, Free University of Berlin, Königin-Luise-Strasse 15, D-14195 Berlin, Germany. Fax: +49 30 838 8445 1902
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Abstract

Background Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder (OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors (SSRJs).

Method The literature is reviewed on knowledge of the role of serotonergic neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid (CSF), various stress neuropeptides, neuroendocrine and behavioural challenge after administration of direct and indirect serotomimetic compounds, and neuroanatomical data on brain circuits organising behaviour.

Results In most of the OCD cases analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations do not significantly differ from age-corrected controls. However, a relationship appears to exist between pre-treatment levels of these metabolites and clinical response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels have been reported in OCD. Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities.

Conclusions We hypothesise that continuous treatment with SSRJs alters serotonin turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain circuits.

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. 13 - 20
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

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References

Aghahanian, G. K. & Andrade, R. (1997) Electrophysiology of 5-HTreceptors. In Handbook of Experimental Pharmacology. Vol. 129: Serotoninergic Neurons and 5-HT Receptors in the CNS (eds Baumgarten, H. G. & Göthert, M.), pp. 499–536. Berlin: Springer-Verlag.Google Scholar
Agren, H., Mefford, I. N., Rudorfer, M. V., et al (1986) Interacting neurotransmitter systems. A non-experimental approach to the 5-HIAA/HVA correlation in human CSF. Journal of Psychiatry Research, 20, 175–193.CrossRefGoogle Scholar
Altemus, M., Pigott, T., L'Heureux, F., et al (1992) Abnormalities in the regulation of vasopressin and corticotropin releasing factor secretion in obsessive–compulsive disorder. Archives of General Psychiatry, 49, 9–20.CrossRefGoogle ScholarPubMed
Altemus, M., Pigott, T., Kalogeras, K. T., et al (1993) CSF somatostatin in obsessive–compulsive disorder. American Journal of Psychiatry, 150, 460–464.Google ScholarPubMed
Altemus, M., Swedo, S. E., Leonard, H. L., et al (1994) Changes in cerebrospinal fluid neurochemistry during treatment of obsessive–compulsive disorder with clomipramine. Archives of General Psychiatry, 51, 794–803.CrossRefGoogle ScholarPubMed
Asberg, M., Ringberger, V.-A., Sjöquist, F., et al (1977) Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine. Clinical Pharmacology and Therapeutics, 21, 201–207.CrossRefGoogle ScholarPubMed
Barr, L. C., Goodman, W. K. & Price, L. H. (1993) The serotonin hypothesis of obsessive compulsive disorder. International Clinical Psychopharmacology, 8, (suppl. 2), 79–82.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Bastani, B., Nash, J. F., Meltzer, H.Y. (1990) Prolactin and cortisol responses to MK-212, a serotonin agonist, in obsessive–compulsive disorder. Archives of General Psychiatry, 47, 833–839.CrossRefGoogle ScholarPubMed
Baumgarten, H. G. & Grozdanovic, Z. (1994) Neuroanatomy and neurophysiology of central serotonergic systems. Journal of Serotonin Research, 1, 171–179.Google Scholar
Baumgarten, H. G. & Grozdanovic, Z. (1995) Psychopharmacology of central serotonergic systems. Pharmacopsychiatry, 28 (suppl. 11), 73–79.CrossRefGoogle ScholarPubMed
Baumgarten, H. G. & Grozdanovic, Z. (1997) Anatomy of central serotoninergic projection systems. In Handbook of Experimental Pharmacology, Vol. 129: Serotoninergic Neurons and 5-HT Receptors in the CNS (eds Baumgarten, H. G. & Göthert, M.), pp. 41–89. Berlin: Springer-Verlag.Google Scholar
Z., Berg, C., Whitaker, A., Davies, M., et al (1988) The survey form of the Leyton Obsessional Inventory – Child Version. Journal of the American Academy of Child and Adolescent Psychiatry, 27, 759–763.Google Scholar
Bertilsson, L., Tuck, J. R. & Siwers, B. (1980) Biochemical effects of zimelidine in man. European journal of Clinical Pharmacology, 18, 483–487.CrossRefGoogle ScholarPubMed
Bjerkenstedt, L., Edman, G., Flyckt, L., et al (1985) Clinical and biochemical effects of citalopram, a selective 5-HTreuptake inhibitor – a dose-response study in depressed patients. Psychopharmacology, 87, 253–259.CrossRefGoogle ScholarPubMed
D., Brewerton, T. (1995) Toward a unified theory of serotonin dysregulation in eating and related disorders. Psychoneuroendocrinology, 20, 561–590.Google Scholar
Brown, S. L. & van Praag, H. M. (eds) (1991) The role of serotonin in psychiatric disorders. Clinical and Experimental Psychiatry Monographs, No 4. New York: Brunner-Mazel Publishers.Google Scholar
Broderick, P. A. & Phelix, C. F. (1997) 1. Serotonin (5-HT) within dopamine reward circuits signals open-field behaviour. Neuroscience and Behavioural Reviews, 21, 227–260.CrossRefGoogle Scholar
Castanon, N., Ramboz, S., Saudou, F., et al (1997) Behavioral consequences of 5-HTIB receptor gene selection. In Handbook of Experimental Pharmacology, Vol. 129: Serotoninergic Neurons and 5-HT Receptors in the CNS (eds Baumgarten, H.G. & Göthert, M.), pp. 351–366. Berlin: Springer-Verlag.Google Scholar
Charney, D. S., Goddman, W. K., Price, L. H., et al (1988) Serotonin function in obsessive–compulsive disorder: a comparison of the effects of tryptophan and m-chlorophenylpiperazine in patients and healthy subjects. Archives of General Psychiatry, 45, 177–185.CrossRefGoogle ScholarPubMed
Dewey, S. L., Smith, G. S., Logan, J., et al (1995) Serotonergic modulation of striatal dopamine measured with positron emission tomography (PET) and in vivo microdialysis. Journal of Neuroscience, 15, 821–829.CrossRefGoogle ScholarPubMed
Dolberg, O. T., Sasson, Y., Cohen, R., et al (1995) The relevance of behavioural probes in obsessive–compulsive disorder. European Neuropsychopharmacoiogy, 5, 161–162.CrossRefGoogle Scholar
Fatemi, S. H., Meltzer, H. Y. & Roth, B. L. (1996) Interaction of atypical antipsychotic drugs with non-dopaminergic systems. In Handbook of Experimental Pharmacology Vol. 120: Antipsychotics (ed. Csernansky, J. G.), pp. 77–115. Berlin: Springer-Verlag.Google Scholar
Fineberg, N. A., Cowen, P. j., Kirk, J. W., et al (1994) Neuroendocrine responses to intravenous L-tryptophan in obsessive compulsive disorder. Journal of Affective Disorders, 32, 97–104.CrossRefGoogle ScholarPubMed
Goodman, W. K. (1992) Pharmacotherapy of obsessive–compulsive disorder. In Zwangsstörungen. Duphar Medical Communication, Band 5 (eds Hand, I., Goodman, W. K. & Evers, U.), pp. 141–151. Berlin: Springer-Verlag.Google Scholar
Goodman, W. K., Price, L. H., Rasmussen, S. A., et al (1989a) The Yale–Brown Obsessive–Compulsive Scale (Y–BOCS): Part I. Development, use and reliability. Archives of General Psychiatry, 46, 1006–1011.CrossRefGoogle Scholar
Goodman, W. K., Price, L. H., Rasmussen, S. A., et al (1989b) Efficacy of fluvoxamine in obsessive–compulsive disorder. A double-blind comparison with placebo. Archives of General Psychiatry, 46, 36–43.CrossRefGoogle ScholarPubMed
Greist, J. H., Jefferson, J.W., Kobak, K. A., et al (1995) Efficacy and tolerability of serotonin transport inhibitors in obsessive–compulsive disorder. Archives of General Psychiatry, 52, 53–60.CrossRefGoogle ScholarPubMed
Greist, J. H. & Jefferson, J.W., (1998) Pharmacotherapy for obsessive compulsive disorder. British Journal Psychiatry, 173 (suppl. 35), 64–70.CrossRefGoogle Scholar
R., Heninger, G. (1995) Indoleamines. The role of serotonin in clinical disorder. In Psychopharmacology. The Fourth Generation of Progress (eds Bloom, F. E. & Kupfer, D.J.), pp. 471–482. New York: Raven Press.Google Scholar
Hewlett, W. A., Vinogradov, S., Berman, S., et al (1992) Fenfluramine stimulation of prolactin in obsessive–compulsive disorder. Psychiatry Research, 42, 81–92.CrossRefGoogle ScholarPubMed
Hollander, E., M., DeCaria, C., Nitescu, A., et al (1992) Serotonergic function in obsessive compulsive disorder: behavioral and neuroendocrine responses to m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers. Archives of General Psychiatry, 49, 21–28.CrossRefGoogle ScholarPubMed
R., Insel, T. & Pickar, D. (1983) Naloxone administration in obsessive–compulsive disorder: report of two cases. American Journal of Psychiatry, 140, 1219–1220.Google Scholar
R., Insel, T., Mueller, E. A., Alterman, I., et al (1985) Obsessive–compulsive disorder and serotonin: is there a connection? Biological Psychiatry, 203, 1174–1188.Google Scholar
Jacobs, B. L. & Fornal, C. A. (1993) 5-HTand motor control: a hypothesis. Trends in Neurosciences, 16, 346–352.CrossRefGoogle Scholar
Kakigi, T., Maeda, K., Kaneda, H., et al (1992) Repeated administration of antidepressant drugs reduces regional somatostatin concentrations in rat brain. Journal of Affective Disorders, 25, 215–220.CrossRefGoogle ScholarPubMed
Kapur, S. & Remington, G. (1996) Serotonin–dopamine interaction and its relevance to schizophrenia. American Journal of Psychiatry, 153, 466–476.Google ScholarPubMed
Kruesi, M. J. P., Swedo, S., Leonard, H., et al (1990) CSF somatostatin in childhood psychiatric disorder: a preliminary investigation. Psychiatry Research, 33, 277–284.CrossRefGoogle ScholarPubMed
Leckman, J. F., Goodman, W. K., North, W. G., et al (1994) Elevated levels of CSF oxytocin in obsessive–compulsive disorder. Archives of General Psychiatry, 51, 782–791.CrossRefGoogle ScholarPubMed
Leckman, J. F., Goodman, W. K., Anderson, G. M., et al (1995) Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls. Neuropsychopharmacology, 12, 73–86.CrossRefGoogle ScholarPubMed
Lee, M. A., Cameron, O. G., Gurguis, G. N. M., et al (1990) α2-Adrenoceptor status in obsessive–compulsive disorder. Biological Psychiatry, 27, 1083–1093.CrossRefGoogle Scholar
Leonard, H. L., Swedo, S. E., Rapoport, J. L., et al (1989) Treatment of obsessive–compulsive disorder with clomipramine and desipramine in children and adolescents. Archives of General Psychiatry, 46, 1088–1092.CrossRefGoogle ScholarPubMed
Lesch, K. P., Hoh, A., Schulte, H. M., et al (1991a) 5-Hydroxytryptamine IA-receptor responsivity in obsessive compulsive disorder, comparison of patients and controls. Archives of General Psychiatry, 48, 540–547 CrossRefGoogle Scholar
Lesch, K. P., Hoh, A., Schulte, H. M., et al (1991b) Long-term fluoxetine treatment decreases 5-HTIA receptor responsivity in obsessive–compulsive disorder. Psychopharmacology, 105, 415–420.CrossRefGoogle Scholar
Linnoila, M., Virkkunen, M., George, T., et al (1993) Impulse control disorders. International Clinical Psychopharmacology, 8 (suppl. 1), 53–56.CrossRefGoogle ScholarPubMed
López-Ibor, J. J. Jr (1988) The involvement of serotonin in psychiatric disorders and behaviour. British Journal of Psychiatry, 153 (suppl. 3), 26–39.CrossRefGoogle Scholar
Lucey, J.V. (1994) Towards a neuroendocrinology of obsessive–compulsive disorder. Journal of Psychopharmacology, 8, 250–257.CrossRefGoogle ScholarPubMed
Lucey, J.V., Butcher, G., Clare, A. W., et al (1992) Busiprione induced prolactin responses in obsessive compulsive disorder. International Clinical Psychopharmacology, 7, 45–49.CrossRefGoogle ScholarPubMed
Lucey, J.V., Butcher, G., Clare, A. W., et al (1994) A pilot study of a neuroendocrine test battery in obsessive compulsive disorder. Journal of Serotonin Research, 1, 73–78.Google Scholar
McBride, P. A., DeMeo, M. D., Sweeney, J. A., et al (1992) Neuroendocrine and behavioral responses to challenge with the indirect serotonin agonist D, L-fenfluramine in adults with obsessive-compulsive disorder. Biological Psychiatry, 31, 19–34.CrossRefGoogle Scholar
McDougle, J. C., Goodman, W. K. & Price, L. H. (1994) Dopamine antagonists in tic-related and psychotic spectrum obsessive compulsive disorder. Journal of Clinical Psychiatry, 55, (suppl. 3), 24–31.Google ScholarPubMed
Maes, M. & Meltzer, H. Y. (1995) The serotonin hypothesis of major depression. In Psychopharmacology The Fourth Generation of Progress (eds Bloom, F. E. & Kupfer, D.J.), pp. 933–944. New York: Raven Press.Google Scholar
Mendlewicz, J. (1992) Efficacy of fluvoxamine in severe depression. Drugs, 43 (suppl. 2), 32–39.CrossRefGoogle ScholarPubMed
Modell, J. G., Mountz, J. M., Curtis, G. C., et al (1989) Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. Journal of Neuropsychiatry, 1, 27–36.Google ScholarPubMed
Montgomery, S. A. (1996) Long-term management of obsessive-compulsive disorder. International Clinical Psychopharmacology, 11 (suppl. 5), 23–29.CrossRefGoogle ScholarPubMed
Murphy, D. L., Pickar, D. & Atterman, I. S. (1982) Methods for the quantitative assessment of depressive and manic behavior. In Techniques for the Evaluation of the Behavior of Psychiatric Patients (eds Burdock, E. I., Sudilovsky, A. & Gershon, S.), pp. 355–392. New York: Marcel Dekker Inc.Google Scholar
Murphy, D. L. & Pigott, T. A. (1990) A comparative examination of a role for serotonin in obsessive compulsive disorder, panic disorder, and anxiety. Journal of Clinical Psychiatry, 51 (suppl. 4), 53–60.Google ScholarPubMed
Price, L. H., Goddard, A. W., Barr, L. C., et al (1995) Pharmacologic challenges in anxiety disorders. In Psychopharmacology. The Fourth Generation of Progress (eds Bloom, F. E. & Kupfer, D. J.), pp. 1311–1323. New York: Raven Press.Google Scholar
Rauch, S. L. & Jenike, M. A. (1993) Neurobiological models of obsessive-compulsive disorder. Psychosomatics, 34, 20–32.CrossRefGoogle ScholarPubMed
Salin, P., Mercugliano, M. & Chesselet, M. F. (1990) Differential effects of chronic treatment with haloperidol and clozapine on the level of preprosomatostatin mRNA in the striatum, nucleus accumbens and frontal cortex of the rat. Cellular and Molecular Neurobiology, 10, 127–144.CrossRefGoogle ScholarPubMed
Smith, C. E., Ware, C. J. & Cowen, P. J. (1991) Pindolol decreases prolactin and growth hormone responses to intravenous L-tryptophan. Psychopharmacology, 103, 140–142.CrossRefGoogle ScholarPubMed
Sorensen, S. M., Kehne, J. H., Fadayl, E. M., et al (1993) Characterization of the 5-HT2 antagonist MDL 100907 as a putative atypical antipsychotic: behavioral, electrophysiological and neurochemical studies. Journal of Pharmacology and Experimental Therapeutics, 266, 684–691.Google ScholarPubMed
Soubrié, P. (1986) Reconciling the role of central serotonin neurons in human and animal behavior. Behavioral and Brain Sciences, 9, 319–364.CrossRefGoogle Scholar
Spoont, M. R. (1992) Modulatory role of serotonin in neural information processing: implications for human psychopathology. Psychological Bulletin, 112, 330–350.CrossRefGoogle ScholarPubMed
Stein, D. J., Spadaccini, E. & Hollander, E. (1995) Meta-analysis of pharmacotherapy trials for obsessive-compulsive disorder. International Clinical Psychopharmacology, 10, 11–18.CrossRefGoogle ScholarPubMed
Sugihara, I., Lang, E. J. & Llinas, R. (1995) Serotonin modulation of inferior olivary oscillations and synchronicity: a multiple-electrode study in the rat cerebellum. European Journal of Neuroscience, 7, 521–534.CrossRefGoogle ScholarPubMed
Swedo, S. E., Leonard, J. L., Kruesi, M. J. P., et al (1992) Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder. Archives of General Psychiatry, 49, 29–36.CrossRefGoogle ScholarPubMed
Törk, I. (1990) Anatomy of the serotonergic system. Annals of the New York Academy of Sciences, 487, 168–174.Google Scholar
Thoren, P., Asberg, M., Cronhol, B., et al (1980a) Clomipramine treatment of obsessive-compulsive disorder. I. A controlled clinical trial. Archives of General Psychiatry, 37, 1281–1285.CrossRefGoogle Scholar
Thoren, P., Asberg, M., Bertilsson, L., et al (1980b) Clomipramine treatment of obsessive-compulsive disorder. II. Biochemical aspects. Archives of General Psychiatry, 37, 1289–1294.CrossRefGoogle ScholarPubMed
Träskman-Bendz, L., Asberg, M. & Bertilsson, L. (1981) Serotonin and noradrenaline uptake inhibitors in the treatment of depression – relationship to 5-HIAA in spinal fluid. Acta Psychiatrica Scandinavica, 63, (suppl. 290), 209–218.CrossRefGoogle Scholar
van de Kar, L. D. & Brownfield, M. S. (1993) Serotonergic neurons and neuroendocrine function. Trends in Pharmacological Sciences, 8, 202–207.Google Scholar
Zohar, J., Mueller, E. A., Insel, T. R., et al (1987) Serotonergic responsivity in obsessive-compulsive disorder. Archives of General Psychiatry, 44, 946–951.CrossRefGoogle ScholarPubMed
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