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European Archives of Psychiatry and Clinical Neuroscience
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience 5/2010

01.08.2010 | Original Paper

Pharmacogenetics of antidepressive treatment

verfasst von: Astrid Zobel, Wolfgang Maier

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 5/2010

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Abstract

The search of the genetic predictors of response to antidepressants is a rapidly expanding field. A large number of clinical studies are reporting partly inconsistent results. Emerging new results focus on new candidate single nucleotide polymorphisms—particularly in the 5HT2a-receptor gene and the gene coding for the co-chaperone FKBP5. The impact of the 5HTTLPR polymorphism on therapeutic outcome and side effects under treatment with SSRIs has to be viewed in a more complex manner than previously proposed. All replicable genetic associations display only a very modest effect. Despite of enormous research efforts, currently pharmacogenetics of therapeutic effects and of side effects of antidepressants are unable to guide decisions on the selection of the most beneficial drug for an individual patient.
Literatur
1.
Arias B, Serretti A, Lorenzi C, Gasto C, Catalan R, Fananas L (2006) Analysis of COMT gene (Val 158 Met polymorphism) in the clinical response to SSRIs in depressive patients of European origin. J Affect Disord 90:251–256CrossRefPubMed
2.
Barton DA, Esler MD, Dawood T, Lambert EA, Haikerwal D, Benchley C, Socratous F, Hastings J, Guo L, Wiesner G, Kaye DM, Bayles R, Schlaich MP, Lambert GW (2008) Elevated brain serotonin turnover in patients with depression. Arch Gen Psychiatry 65:38–46CrossRefPubMed
3.
Baune BT, Hohoff C, Mortensen LS, Deckert J, Arolt V, Domschke K (2008) Serotonin transporter polymorphism (5-HTTLPR) association with melancholic depression: a female specific effect? Depress Anxiety 25:920–925CrossRefPubMed
4.
Baune BT, Hohoff C, Roehrs T, Deckert J, Arolt V, Domschke K (2008) Serotonin receptor 1A–1019C/G variant: impact on antidepressant pharmacoresponse in melancholic depression? Neurosci Lett 436:111–115CrossRefPubMed
5.
Baune BT, Hohoff C, Berger K, Neumann A, Mortensen S, Roehrs T, Deckert J, Arolt V, Domschke K (2009) Association of the COMT val158met variant with antidepressant treatment response in major depression. Neuropsychopharmacology 33:924–932CrossRef
6.
Béïque JC, Blier P, de Montigny C, Debonnel G (2000) Potentiation by (−)Pindolol of the activation of postsynaptic 5-HT (1A) receptors induced by venlafaxine. Neuropsychopharmacology 23:294–306CrossRefPubMed
7.
Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Putz B, Papiol S, Seaman S, Lucae S, Kohli MA, Nickel T, Kunzel HE, Fuchs B, Majer M, Pfennig A, Kern N, Brunner J, Modell S, Baghai T, Deiml T, Zill P, Bondy B, Rupprecht R, Messer T, Kohnlein O, Dabitz H, Bruckl T, Muller N, Pfister H, Lieb R, Mueller JC, Lohmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B (2004) Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 36:1319–1325CrossRefPubMed
8.
Choi MJ, Kang RH, Lim SW, Oh KS, Lee MS (2006) Brain-derived neurotrophic factor gene polymorphism (Val66Met) and citalopram response in major depressive disorder. Brain Res 1118:176–182CrossRefPubMed
9.
Domschke K, Lawford B, Laje G, Berger K, Morris P, Deckert J, Arolt V, McMahon FJ, Baune BT (2009) Brain-derived neurotrophic factor (BDNF) gene: no major impact on antidepressant treatment response. Int J Neuropsychopharmacol 23:1–9
10.
Franchini L, Serretti A, Gasprini M, Smeraldi E (1998) Familial concordance of fluvoxamine response as a tool for differentiating mood disorder pedigrees. J Psychiatr Res 32:255–259CrossRefPubMed
11.
Gratacos M, Soria V, Urretavizcaya M, Gonzalex JR, Crespo JM, Bayes M, de Cid R, Menchón JM, Vallejo J, Estivill X (2008) A brain-derived neurotrophic factor (BDNF) haplotype is associated with antidepressant treatment outcome in mood disorders. Pharmacogenomics J 8:101–112CrossRefPubMed
12.
Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR (2005) A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 62:146–152CrossRefPubMed
13.
Holsboer F (2001) Antidepressant drug discovery in the postgenomic era. World J Biol Psychiatry 2:165–177CrossRefPubMed
14.
Hong C-J, Chen T-J, Yu YW-Y, Tsai S-J (2006) Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder. Pharmacogenomics J 6:27–33CrossRefPubMed
15.
Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Tabuman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006) Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 78:815–826CrossRefPubMed
16.
Hu XZ, Rush AJ, Charney D, Wilson AF, Sorant AJM, Papnicolaou GJ, Fava M, Trivedi MH, Wisniewski SR, Laje G, Paddock S, McMahon FJ, Manji H, Lipsky RH (2007) Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression. Arch Gen Psychiatry 64:783–792CrossRefPubMed
17.
Huezo-Diaz P, Uher R, Smith R, Rietschel M, Henigsberg N, Marusic A, Mors O, Maier W, Hauser J, Souery D, Placentino A, Zobel A, Larsen EJ, Czerski PM, Gupta G, Hoda F, Perroud N, Farmer A, Craig I, Aitchison KJ, McGuffin P (2009) Moderation of antidepressant response by the serotonin transporter gene. Br J Psychiatry 194:30–38CrossRef
18.
Ising M, Lucae S, Binder EB, Bettecken T, Uhr M, Ripke S, Kohli MA, Hennings JM, Horstmann S, Kloiber S, Menke A, Bondy B, Rupprecht R, Domschke K, Baune BT, Arolt V, Rush AJ, Holsboer F, Müller-Myhsok B (2009) A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression. Arch Gen Psychiatry 66:966–975CrossRefPubMed
19.
Kato M, Serretti A (2008) Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry (Nov. 4, 2008 ahead of print)
20.
Kim H, Lim SW, Kim S, Kim JW, Chang YH, Carroll BJ, Kim DK (2006) Monoamine transporter gene polymorphisms and antidepressant response in Koreans with late-life depression. JAMA 296:1609–1618CrossRefPubMed
21.
Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmöller J (2004) Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug respone. Mol Psychiatry 9:442–473CrossRefPubMed
22.
Kirchheiner J, Lorch R, Lebedeva E, Seeringer A, Roots I, Sasse J, Brockmöller J (2008) Genetic variants in FKBP5 affecting response to antidepressant drug treatment. Pharmacogenomics 9:841–846CrossRefPubMed
23.
Kraft JB, Slager SL, McGrath PJ, Hamilton SP (2005) Sequence analysis of the serotonin transporter and associations with antidepressant response. Biol Psychiatry 58:374–381CrossRefPubMed
24.
Laje G, McMahon FJ (2008) The pharmacogenetics of major depression: past, present, and future. Biol Psychiatry 62:1205–1207CrossRef
25.
Lambert G, Johansson M, Ägren H, Friberg P (2000) Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness. Arch Gen Psychiatry 57:787–793CrossRefPubMed
26.
Landen M, Thase ME (2006) A model to explain the therapeutic effects of serotonin reuptake inhibitors: the role of 5-HT2 receptors. Psychopharmacol Bull 39:147–166PubMed
27.
Lane P (2008) Handling drop-out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches. Pharm Stat 7:93–106CrossRefPubMed
28.
Lee M, Bailer UF, Frank GK, Henry SE, Meltzer CC, Price JC, Mathis CA, Putnam KT, Ferrell RE, Hariri AR, Kaye WH (2005) Relationship of a 5-HT transporter functional polymorphism to 5-HT1A receptor binding in healthy women. Mol Psychiatry 10:715–716CrossRefPubMed
29.
Lekman M, Laje G, Charney D, John Rush A, Wilseon AF, Sorand AJM, Lipsky R, Wisniewski SR, Manji H, McMahon FJ, Paddock S (2008) The FKBP5-gene in depression and treatment response–an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort. Biol Psychiatry 63:1103–1110CrossRefPubMed
30.
Lemonde S, Du L, Bakish D, Hrdina P, Albert P (2004) Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response. Int J Neuropsychopharmacol 7:501–506CrossRefPubMed
31.
32.
Licinio J, O’Kirwan F, Irizarry K, Merriman B, Thakur S, Jepson R, Lake S, Tantisira KG, Weiss ST, Wong ML (2004) Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans. Mol Psychiatry 9:1075–1082CrossRefPubMed
33.
Liu Z, Zhu F, Wang G, Xiao Z, Tang J, Liu W, Wang H, Liu H, Wang X, Wu Y, Cao Z, Li W (2007) Association study of corticotropin-releasing hormone receptor1 gene polymorphisms and antidepressant response in major depressive disorders. Neurosci Lett 414:155–158CrossRefPubMed
34.
Martin J, Cleak J, Willis-Owen SAG (2007) Mapping regulatory variants for the serotonin transporter gene based on allelic expression imbalance. Mol Psychiatry 12:421–422CrossRefPubMed
35.
Martinowich K, Manji H, Lu B (2007) New insights into BDNF function in depression and anxiety. Nat Neurosci 10:1089–1093CrossRefPubMed
36.
McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, Sorant AJ, Papanicolaou GJ, Laje G, Fava M, Trivedi MH, Wisniewski SR, Manji H (2006) Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet 78:804–814CrossRefPubMed
37.
Mössner R, Daniel S, Albert D, Heils A, Okladnova O, Schmitt A, Lech KP (2000) Serotonin transporter function is modulated by brain derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochem Int 36:197–202CrossRefPubMed
38.
Mrazek DA, Rush AJ, Biernacka JM, O’Kane DJ, Cunningham JM, Wieben ED, Schaid DJ, Drews MS, Courson V, Snyder KA, Black JL, Weinshilboum RM (2009) SLC6A4 variation and citalopram response. Am J Med Genet B Neuropsychiatr Genet 50B:341–351
39.
Murphy GM Jr, Hollander SB, Rodrigues HE, Kremer C, Schatzberg AF (2004) Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Arch Gen Psychiatry 61:1163–1169CrossRefPubMed
40.
Nakamura M, Ueno S, Sano A, Tanabe H (2000) The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5:32–38CrossRefPubMed
41.
Nierenberg AA (2003) Predictors of response to antidepressants: general principles and clinical implications. Psychiatr Clin North Am 26:345–352CrossRefPubMed
42.
Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJM, Lipsky R, Wisniewski SR, Manji H, McMahon FJ (2007) Association of GRIK4 with outcome of antidepressant treatment in the STAR*D Cohort. Am J Psychiatry 164:1181–1188CrossRefPubMed
43.
Parsons MJ, D’Souza UM, Arranz MJ, Kerwin RW, Makoff AJ (2004) The -1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity. Biol Psychiatry 56:406–410CrossRefPubMed
44.
Perlis RH, Fijal B, Adams DH, Sutton VK, Trivedi MH, Houston JP (2009) Variation in catechol-o-methyltransferase is associated with duloxetine response in a clinical trial for major depressive disorder. Biol Psychiatry 65:785–791CrossRefPubMed
45.
Peters EJ, Slager SL, McGrath PJ, Knowles JA, Hamilton SP (2004) Investigation of serotonin-related genes in antidepressant response. Mol Psychiatry 9:879–889CrossRefPubMed
46.
Rush AJ, Kraemer HC, Sackeim HA, Fava M, Trivedi MH, Ninan FrankE, PT ThaseME, Gelenberg AJ, Kupfer DJ, Regier DA, Rosenbaum JF, Ray O, Schatzberg AF ACNP, Force Task (2006) Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology 31:1841–1853CrossRefPubMed
47.
Sen S, Nesse RM, Stoltenberg SF, Li S, Gleiberman L, Chakravarti A (2003) A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology 28:397–401CrossRefPubMed
48.
Serretti A, Artioli P, Lorenzi C, Pirovano A, Tubazio V, Zanardi R (2004) The C(-1019)G polymorphism of the 5-HT1A gene promoter and antidepressant response in mood disorders: preliminary findings. Int J Neuropsychopharmacol 7:453–460CrossRefPubMed
49.
Serretti A, Kato M, De RD, Kinoshita T (2007) Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Mol Psychiatry 12:247–257PubMed
50.
Serretti A, Mandelli L, Lorenzi C, Pirovano A, Oligiati P, Colombo C, Smeraldi E (2007) Serotonin transporter gene influences the thime course of improvement of “core” depressive and somatic anxiety symptoms during treatment with SSRIs for recurrent mood disorders. Psychiatry Res 149:185–193CrossRefPubMed
51.
Szegedi A, Rujescu D, Tadic A, Muller MJ, Kohnen R, Stassen HH, Dahmen N (2005) The catechol-o-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtrazapine, but not to paroxetine in major depression. Pharmacogenomics 5:49–53CrossRef
52.
Trivedi MH, Daly EJ (2007) Measurement-based care for refractory depression: a clinical decision support model for clinical research and practice. Drug Alcohol Depend 88(Suppl2):S61–S71CrossRefPubMed
53.
Tsai SJ, Cheng CY, Yu YW, Chen TJ, Hong CJ (2003) Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response. Am J Med Genet 123B:19–22CrossRefPubMed
54.
Uher R, Farmer A, Maier W, Rietschel M, Hauser J, Marusic A, Mors O, Elkin A, Williamson RJ, Schmael C, Henigsberg N, Perez J, Mendlewicz J, Janzing JG, Zobel A, Skibinska M, Kozel D, Stamp AS, Bajs M, Placentino A, Barreto M, McGuffin P, Aitchison KJ (2008) Measuring depression: comparison and integration of three scales in the GENDEP study. Psychol Med 38:289–300CrossRefPubMed
55.
Uher R, Maier W, Hauser J, Marusic A, Schmael C, Mors O, Henigsberg N, Souery D, Placentino A, Rietschel M, Zobel A, Dmitrzak-Weglarz M, Petrovic A, Jorgensen L, Kalember P, Giovannini C, Barreto M, Elkin A, Landau S, Farmer A, Aitchison KJ, McGuffin P (2009) Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. Br J Psychiatry 194:252–259CrossRefPubMed
56.
Uher R, Huezo-Diaz P, Perroud N, Smith R, Rietchel M, Mors O, Hauser J, Maier W, Kozel D, Henigsberg N, Barreto M, Placentino A, Dernovsek MZ, Schulze TG, Kalember P, Zobel A, Czerski PM, Larsen ER, Sourey D, Giovannini C, Gray JM, Lewis CM, Farmer A, Aitchison KJ, McGuffin P, Craig I (2009) Genetic predictors of response to antidepressants in the GENDEP project. Pharmacogenomics J 9:225–233CrossRefPubMed
57.
Uhr M, Tontsch A, Namendorf C, Ripke S, Lucae S, Ising M, Dose T, Ebinger M, Rosenhagen M, Kohli M, Kloiber S, Salyakina D, Bettecken T, Specht M, Pütz B, Binder EB, Müller-Myhsok B, Holsboer F (2008) Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron 57:203–209CrossRefPubMed
58.
Van Rossum EF, Binder EB, Majer M, Koper JW, Ising M, Modell S, Salyakina D, Lamberts SW, Holsboer F (2006) Polymorphisms of the glucocorticoid receptor gene and major depression. Biol Psychiatry 59:681–688CrossRefPubMed
59.
Wang JW, Dranovsky A, Hen R (2008) The when and where of BDNF and the antidepressant response. Biol Psychiatry 63:640–641CrossRefPubMed
60.
Wilkie MJV, Smith G, Day RK, Matthews K, Smith D, Blackwood D, Reid IC, Wolf CR (2009) Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. Pharmacogenenomics J 9:61–70CrossRef
61.
Yoshida K, Higuchi H, Kamata M, Takahashi H, Inoue K, Suzuki T, Itoh K, Ozaki N (2007) The G196A polymorphism of the brain-derived neurotrophic factor gene and the antidepressant effect of milnacipran and fluvoxamine. J Psychopharmacol 21:650–656CrossRefPubMed
62.
Yoshida K, Higuchi H, Takahashi H, Kamata M, Sato K, Inoue K, Suzuki T, Itoh K, Ozaki N (2008) Influence of the tyrosine hydoxylase val81met polymorphism and catechol-O-methyltransferase val158met polymorphism on the antidepressant effect of milnacipran. Hum Pychopharmacol 23:121–128CrossRef
63.
Zobel A, Schuhmacher A, Jessen F, Höfels S, von Widdern O, Metten M, Pfeiffer U, Hanses C, Becker T, Rietschel M, Scheef L, Block W, Schild HH, Maier W, Schwab SG (2009) DNA-sequence variants of the FKBP5 gene are associated with diagnosis and intermediate phenotypes of unipolar depression. Int J Neuropsychopharmacol (in press)
Metadaten
Titel
Pharmacogenetics of antidepressive treatment
verfasst von
Astrid Zobel
Wolfgang Maier
Publikationsdatum
01.08.2010
Verlag
Springer-Verlag
Erschienen in
European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 5/2010
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-009-0091-4

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