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Serotonin Related Genes Affect Antidepressant Treatment in Obsessive–Compulsive Disorder

Published online by Cambridge University Press:  12 December 2007

F. Van Nieuwerburgh ,
D. Deforce  and
D.A.J.P. Denys
F. Van Nieuwerburgh
Affiliation:
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium; Email: Filip.VanNieuwerburgh@UGent.be
D. Deforce
Affiliation:
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium; Email: Dieter.Deforce@Ugent.be
D.A.J.P. Denys
Affiliation:
AMC, University of Amsterdam, Amsterdam, The Netherlands; Email: D.Denys@amc.nl
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Extract

ABSTRACT

Up to 60% of OCD patients do not respond to a regular serotonin reuptake inhibitor (SRI) treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT1Dβ, and 5-HT2A receptor genes affect the efficacy of SRI treatment in OCD. Ninety-one outpatients with primary OCD according to DSM-IV criteria consented to the study were randomly assigned a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine, or 60 mg/day of paroxetine. Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive–compulsive scale (Y-BOCS), and response was defined as a ≥25% reduction on the Y-BOCS. All of the paroxetine treated patients, with the G/G genotype of the 5-HT2A polymorphism were responders (χ2 = 8.66, df = 2, p = 0.013). In the venlafaxine treated patients, the majority of responders carried the S/L genotype of the 5-HTTLPR polymorphism (χ2 = 9.71, df = 2, p = 0.008). The small group of patients who both carried the S/L genotype of the 5-HTTLPR polymorphism and the G/G genotype of the 5-HT2A polymorphism responded all to treatment.

The results of this study suggest that the response in paroxetine and in venlafaxine treated OCD patients is associated with the G/G genotype of the 5-HT2A polymorphism and with the S/L genotype of the 5-HTTLPR polymorphism, respectively.

Keywords

5-HT1Dβ5-HT2A5-HTT5-HTTLPRassociation studyobsessive–compulsive disorderpharmacogeneticsserotoninserotonin reuptake inhibitorSSRI
Type
Research Article
Information
Progress in Neurotherapeutics and Neuropsychopharmacology , Volume 3 , Issue 1 , January 2008 , pp. 227 - 240
Copyright
© 2008 Cambridge University Press

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References

Billett, E.A., Richter, M.A., King, N., Heils, A., Lesch, K.P., & Kennedy, J.L. (1997). Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Molecular Psychiatry, 2 (Suppl. 5), 403–406.Google Scholar
Bray, N.J., Buckland, P.R., Hall, H., Owen, M.J., & O'Donovan, M.C. (2004). The serotonin-2A receptor gene locus does not contain common polymorphism affecting mRNA levels in adult brain. Molecular Psychiatry, 9, 109–114.Google Scholar
Denys, D., Burger, H., van Megen, H., de Geus, F., & Westenberg, H. (2003a). A score for predicting response to pharmacotherapy in obsessive–compulsive disorder. International Clinical Psychopharmacology, 18 (Suppl. 6), 315–322.Google Scholar
Denys, D., van der Wee, N., van Megen, H.J.G.M., & Westenberg, H.G.M. (2003b). A double blind comparison of venlafaxine and paroxetine in obsessive–compulsive disorder. Journal of Clinical Psychopharmacology, 23 (Suppl. 6), 568–575.Google Scholar
Denys, D., van Megen, H.J.G.M., van der Wee, N., & Westenberg, H.G.M. (2004). A double-blind switch study of paroxetine and venlafaxine in obsessive–compulsive disorder. Journal of Clinical Psychiatry, 65 (Suppl. 1), 37–43.Google Scholar
Di Bella, D., Erzegovesi, S., Cavallini, M.C., d'Annucci, A., & Bellodi, L. (2000). Obsessive–compulsive disorder, treatment response and the 5htt gene. American Journal of Medical Genetics, 96 (Suppl. 4), 536–536.Google Scholar
Elmansari, M., Bouchard, C., & Blier, P. (1995). Alteration of serotonin release in the guinea-pig orbitofrontal cortex by selective serotonin reuptake inhibitors – relevance to treatment of obsessive–compulsive disorder. Neuropsychopharmacology, 13 (Suppl. 2), 117–127.Google Scholar
Goodman, W.K., Price, L.H., Rasmussen, S.A., Mazure, C., Fleischmann, R.L., Hill, C.L., Heninger, G.R., & Charney, D.S. (1989). The yale-brown obsessive compulsive scale. 1. Development, use, and reliability. Archives of General Psychiatry, 46 (Suppl. 11), 1006–1011.Google Scholar
Goodman, W.K., Ward, H.E., & Murphy, T.K. (1998). Biologic approaches to treatment-refractory obsessive–compulsive disorder. Psychiatric Annals, 28 (Suppl. 11), 641–649.Google Scholar
Hamilton, M. (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology, 32, 50–55.Google Scholar
Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23, 56–62.Google Scholar
Heinz, A., Jones, D.W., Mazzanti, C., Goldman, D., Ragan, P., Hommer, D., Linnoila, M., & Weinberger, D.R. (2000). A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biological Psychiatry, 47 (Suppl. 7), 643–649.Google Scholar
Hollander, E., Bienstock, C.A., Koran, L.M., Pallanti, S., Marazziti, D., Rasmussen, S.A., Ravizza, L., Benkelfat, C., Saxena, S., Greenberg, B.D., Sasson, Y., & Zohar, J. (2002). Refractory obsessive–compulsive disorder: state-of-the-art treatment. Journal of Clinical Psychiatry, 63, 20–29.Google Scholar
Li, Q., Muma, N.A., Battaglia, G., & Van der Kar, L.D. (1997). Fluoxetine gradually increases [i-125]doi-labelled 5-ht2a/2c receptors in the hypothalamus without changing the levels of g(q)- and g(11)-proteins. Brain Research, 775 (Suppl. 1–2), 225–228.Google Scholar
Mancama, D., & Kerwin, R.W. (2003). Role of pharmacogenomics in individualising treatment with ssris. CNS Drugs, 17 (Suppl. 3), 143–151.Google Scholar
Mann, J.J., Huang, J.Y., Underwood, M.D., Kassir, S.A., Oppenheim, S., Kelly, T.M., Dwork, A.J., & Arango, V. (2000). A serotonin transporter gene promoter polymorphism (5-httlpr) and prefrontal cortical finding in major depression and suicide. Archives of General Psychiatry, 57 (Suppl. 8), 729–738.Google Scholar
Massou, J.M., Trichard, C., AttarLevy, D., Feline, A., Corruble, E., Beaufils, B., & Martinot, J.L. (1997). Frontal 5-ht2a receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors. Psychopharmacology, 133 (Suppl. 1), 99–101.Google Scholar
McDougle, C.J., Epperson, C.N., Price, L.H., & Gelernter, J. (1998). Evidence for linkage disequilibrium between serotonin transporter protein gene (slc6a4) and obsessive compulsive disorder. Molecular Psychiatry, 3 (Suppl. 3), 270–273.Google Scholar
Meyer, J.H., Kapur, S., Eisfeld, B., Brown, G.M., Houle, S., DaSilva, J., Wilson, A.A., Rafi-Tari, S., Mayberg, H.S., & Kennedy, S.H. (2001). The effect of paroxetine on 5-ht2a receptors in depression: an [f-18]setoperone pet imaging study. American Journal of Psychiatry, 158 (Suppl. 1), 78–85.Google Scholar
Nakamura, T., Matsushita, S., Nishiguchi, N., Kimura, M., Yoshino, A., & Higuchi, S. (1999). Association of a polymorphism of the 5ht2a receptor gene promoter region with alcohol dependence. Molecular Psychiatry, 4 (Suppl. 1), 85–88.Google Scholar
Naylor, L., Dean, B., Pereira, A., Mackinnon, A., Kouzmenko, A., & Copolov, D. (1998). No association between the serotonin transporter-linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus. Molecular Medicine, 4 (Suppl. 10), 671–674.Google Scholar
Rioux, A., Fabre, V., Lesch, K.P., Moessner, R., Murphy, D.L., Lanfumey, L., Hamon, M., & Martres, M.P. (1999). Adaptive changes of serotonin 5-ht2a receptors in mice lacking the serotonin transporter. Neuroscience Letters, 262 (Suppl. 2), 113–116.Google Scholar
Sato, K., Yoshida, K., Takahashi, H., Ito, K., Kamata, M., Higuchi, H., Shimizu, T., Itoh, K., Inoue, K., Tezuka, T., Suzuki, T., Ohkubo, T., Sugawara, K., & Otani, K. (2002). Association between-1438g/a promoter polymorphism in the 5-ht2a receptor gene and fluvoxamine response in Japanese patients with major depressive disorder. Neuropsychobiology, 46 (Suppl. 3), 136–140.Google Scholar
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., Hergueta, T., Baker, R., & Dunbar, G.C. (1998). The mini-international neuropsychiatric interview (mini): The development and validation of a structured diagnostic psychiatric interview for dsm-iv and icd-10. Journal of Clinical Psychiatry, 59, 22–33.Google Scholar
Shioe, K., Ichimya, T., Suhara, T., Takano, A., Sudo, Y., Yasuno, F., Hirano, M., Shinohara, M., Kagami, A., Okubo, Y., Nankai, M., & Kanba, S. (2003). No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by pet. Synapse, 48 (Suppl. 4), 184–188.Google Scholar
Spurlock, G., Heils, A., Holmans, P., Williams, J., D'Souza, U.M., Cardno, A., Murphy, K.C., Jones, L., Buckland, P.R., McGuffin, P., Lesch, K.P., & Owen, M.J. (1998). A family based association study of t102c polymorphism in 5ht2a and schizophrenia plus identification of new polymorphisms in the promoter. Molecular Psychiatry, 3 (Suppl. 1), 42–49.Google Scholar
Smith, G.S., Lotrich, F.E., Malhotra, A.K., Lee, A.T., Ma, Y.L., Kramer, E., Gregersen, P.K., Eidelberg, D., & Pollock, B.G. (2004). Effects of serotonin transporter promoter polymorphisms on serotonin function. Neuropsychopharmacology, 29 (Suppl. 12), 2226–2234.Google Scholar
Smits, K.M., Smits, L.J.M., Schouten, J.S.A.G., Stelma, F.F., Nelemans, P., & Prins, M.H. (2004). Influence of sertpr and stin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic review. Molecular Psychiatry, 9 (Suppl. 5), 433–441.Google Scholar
Tot, S., Erdal, M.E., Yazici, K., Yazici, A.E., & Metin, O. (2003). T102c and -1438 g/a polymorphisms of the 5-ht2a receptor gene in turkish patients with obsessive–compulsive disorder. European Psychiatry, 18 (Suppl. 5), 249–254.Google Scholar
Turecki, G., Briere, R., Dewar, K., Antonetti, T., Lesage, A.D., Seguin, M., Chawky, N., Vanier, C., Alda, M., Joober, R., Benkelfat, C., & Rouleau, G.A. (1999). Prediction of level of serotonin 2a receptor binding by serotonin receptor 2a genetic variation in postmortem brain samples from subjects who did or did not commit suicide. American Journal of Psychiatry, 156 (Suppl. 9), 1456–1458.Google Scholar
Van Dyck, C.H., Malison, R.T., Staley, J.K., Jacobsen, L.K., Seibyl, J.P., Laruelle, M., Baldwin, R.M., Innis, R.B., & Gelernter, J. (2004). Central serotonin transporter availability measured with [i-123]beta-cit spect in relation to serotonin transporter genotype. American Journal of Psychiatry, 161 (Suppl. 3), 525–531.Google Scholar
Veenstra-VanderWeele, J., Anderson, G.M., & Cook, E.H. (2000). Pharmacogenetics and the serotonin system: initial studies and future directions. European Journal of Pharmacology, 410 (Suppl. 2–3), 165–181.Google Scholar
Willeit, M., Stastny, J., Pirker, W., Praschak-Rieder, N., Neumeister, A., Asenbaum, S., Tauscher, J., Fuchs, K., Sieghart, W., Hornik, K., Aschauer, H.N., Brucke, T., & Kasper, S. (2001). No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism. Biological Psychiatry, 50 (Suppl. 1), 8–12.Google Scholar
Williams, R.B., Marchuk, D.A., Gadde, K.M., Barefoot, J.C., Grichnik, K., Helms, M.J., Kuhn, C.M., Lewis, J.G., Schanberg, S.M., Stafford-Smith, M., Suarez, E.C., Clary, G.L., Svenson, I.K., & Siegler, I.C. (2003). Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology, 28 (Suppl. 3), 533–541.Google Scholar