Do we need pharmacogenetics to personalize antidepressant therapy?

Cellular and Molecular Life Sciences

Volumn 70, Issue 18, 2013, Pages 3327-3340

  Lanni, Cristina ^a   Racchi, Marco ^a   Govoni, Stefano ^a  

^a SCUOLA UNIVERSITARIA SUPERIORE IUSS PAVIA   (Italy)

Author keywords

Adverse effects; Antidepressant treatment; Pharmacodynamics; Pharmacokinetics; Polymorphisms; Suicidal behavior

Indexed keywords

ANTIDEPRESSANT AGENT; BRAIN DERIVED NEUROTROPHIC FACTOR; CITALOPRAM; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; DESIPRAMINE; DIAZEPAM; ESCITALOPRAM; FLIBANSERIN; FLUOXETINE; FLUVOXAMINE; MILNACIPRAN; MIRTAZAPINE; MONOAMINE OXIDASE INHIBITOR; MULTIDRUG RESISTANCE PROTEIN; NEFAZODONE; NORADRENALIN TRANSPORTER; NORTRIPTYLINE; PAROXETINE; SEROTONIN 1A RECEPTOR; SEROTONIN 2A RECEPTOR; SEROTONIN 3A RECEPTOR; SEROTONIN NORADRENALIN REUPTAKE INHIBITOR; SEROTONIN TRANSPORTER; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRICYCLIC ANTIDEPRESSANT AGENT; TRYPTOPHAN HYDROXYLASE; UNINDEXED DRUG; VENLAFAXINE;

ANTIDEPRESSANT ACTIVITY; CARDIOTOXICITY; CLINICAL TRIAL (TOPIC); DEPRESSION; DISEASE PREDISPOSITION; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG TARGETING; DRUG WITHDRAWAL; GENETIC DIFFERENCE; HUMAN; NAUSEA; PERSONALIZED MEDICINE; PHARMACOGENETICS; PROMOTER REGION; REMISSION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SUICIDAL BEHAVIOR; SUICIDAL IDEATION; SUICIDE; SUICIDE ATTEMPT; TREATMENT FAILURE; TREATMENT OUTCOME; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

ANTIDEPRESSIVE AGENTS; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP2D6; DEPRESSION; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; P-GLYCOPROTEIN; PHARMACOGENETICS; POLYMORPHISM, GENETIC; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SUICIDE; TRYPTOPHAN HYDROXYLASE;

EID: 84883466355     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-012-1237-5     Document Type: Review

References (115)

1. Hamet P, Tremblay J (2005) Genetics and genomics of depression. Metabolism 54:10-15
2. Lanni C, Govoni S, Lucchelli A, Boselli C (2009) Depression and antidepressants: molecular and cellular aspects. Cell Mol Life Sci 66:2985-3008
3. Franchini L, Serretti A, Gasperini M, Smeraldi E (1998) Familial concordance of fluvoxamine response as a tool for differentiating mood disorder pedigrees. J Psychiatr Res 32:255-259
4. Evans WE, McLeod HL (2003) Pharmacogenomics - drug disposition, drug targets, and side effects. N Engl J Med 348:538-549
5. Kato M, Serretti A (2010) Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry 15:473-500
6. Uher R, Huezo-Diaz P, Perroud N, Smith R, Rietschel M, Mors O, Hauser J, Maier W, Kozel D, Henigsberg N, Barreto M, Placentino A, Dernovsek MZ, Schulze T, Kalember P, Zobel A, Czerski P, Larsen ER, Souery D, Govannini C, Gray JM, Lewis CM, Farmer A, Aitchison KJ, McGuffin P, Craig I (2009) Genetic predictors of antidepressant response in the GENDEP project. Pharmacogenomics J 9:225-233
7. Shah RR (2005) Pharmacogenetics in drug regulation: promise, potential and pitfalls. Philos Trans R Soc Lond B 360:1617-1638
8. Tomalik-Scharte D, Lazar A, Fuhr U, Kirchheiner J (2008) The clinical role of genetic polymorphisms in drug-metabolizing enzymes. Pharmacogenomics J 8:4-15
9. Ingelman-Sundberg M (2005) Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 5:6-13
10. Bradford LD (2002) CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 3:229-243
11. Fukuda T, Yamamoto I, Nishida Y, Zhou Q, Ohno M, Takada K, Azuma J (1999) Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers. Br J Clin Pharmacol 47:450-453
12. Dalén P, Dahl ML, Bernal Ruiz MLB, Nordin J, Bertilsson L (1998) 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin Pharmacol Ther 63:444-452
13. Sachse C, Brockmöller J, Bauer S, Roots I (1997) Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 60:284-295
14. Lessard E, Yessine MA, Hamelin BA, O'Hara G, LeBlanc J, Turgeon J (1999) Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics 9(4):435-443
15. Mulder H, Herder A, Wilmink FW, Tamminga WJ, Belitser SV, Egberts AC (2006) The impact of cytochrome P450-2D6 genotype on the use and interpretation of therapeutic drug monitoring in long-stay patients treated with antidepressant and antipsychotic drugs in daily psychiatric practice. Pharmacoepidemiol Drug Saf 15:107-114
16. McAlpine DE, O'Kane DJ, Black JL, Mrazek DA (2007) Cytochrome P450 2D6 genotype variation and venlafaxine dosage. Mayo Clin Proc 82:1065-1068
17. Mulder H, Wilmink FW, Beumer TL, Tamminga WJ, Jedema JN, Egberts AC (2005) The association between cytochrome P450 2D6 genotype and prescription patterns of antipsychotic and antidepressant drugs in hospitalized psychiatric patients: a retrospective follow-up study. J Clin Psychopharmacol 25:188-191
18. Bijl MJ, Visser LE, Hofman A, Vulto AG, van Gelder T, Stricker BH, van Schaik RH (2008) Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants. Br J Clin Pharmacol 65:558-564
19. Murphy GM Jr, Kremer C, Rodrigues HE, Schatzberg AF (2003) Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry 160:1830-1835
20. Rudberg I, Hermann M, Refsum H, Molden E (2008) Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. Eur J Clin Pharmacol 64:1181-1188
21. Rudberg I, Mohebi B, Hermann M, Refsum H, Molden E (2008) Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients. Clin Pharmacol Ther 83:322-327
22. Yin OQ, Wing YK, Cheung Y, Wang ZJ, Lam SL, Chiu HF, Chow MS (2006) Phenotype-genotype relationship and clinical effects of citalopram in Chinese patients. J Clin Psychopharmacol 26:367-372
23. Fukasawa T, Suzuki A, Otani K (2007) Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. J Clin Pharmacol Ther 32:333-341
24. Sim SC, Nordin L, Andersson TM, Virding S, Olsson M, Pedersen NL, Ingelman-Sundberg M (2010) Association between CYP2C19 polymorphism and depressive symptoms. Am J Med Genet B Neuropsychiatr Genet 153B:1160-1166
25. Fradette C, Yamaguchi N, Du Souich P (2004) 5-Hydroxytryptamine is biotransformed by CYP2C9, 2C19 and 2B6 to hydroxylamine, which is converted into nitric oxide. Br J Pharmacol 141:407-414
26. Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM (1999) Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 39:361-398
27. Callen DF, Baker E, Simmers RN, Seshadri R, Roninson IB (1987) Localization of the human multiple drug resistance gene, MDR1, to 7q21.1. Hum Genet 77:142-144
28. Schinkel AH, Jonker JW (2003) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 55:3-29
29. Horstmann S, Binder EB (2009) Pharmacogenomics of antidepressant drugs. Pharmacol Ther 124:57-73
30. Rochat B, Baumann P, Audus KL (1999) Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium. Brain Res 831:229-236
31. Crisafulli C, Fabbri C, Porcelli S, Drago A, Spina E, De Ronchi D, Serretti A (2011) Pharmacogenetics of antidepressants. Front Pharmacol 2:6
32. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmöller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 97:3473-3478
33. Sakurai A, Onishi Y, Hirano H, Seigneuret M, Obanayama K, Kim G, Liew EL, Sakaeda T, Yoshiura K, Niikawa N, Sakurai M, Ishikawa T (2007) Quantitative structure-activity relationship analysis and molecular dynamics simulation to functionally validate nonsynonymous polymorphisms of human ABC transporter ABCB1 (P-glycoprotein/MDR1). Biochemistry 46:7678-7693
34. Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM (2007) A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science 315:525-528
35. 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 57:203-209
36. Peters EJ, Slager SL, Kraft JB, Jenkins GD, Reinalda MS, McGrath PJ, Hamilton SP (2008) Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS ONE 3:e1872
37. Kato M, Fukuda T, Serretti A, Wakeno M, Okugawa G, Ikenaga Y, Hosoi Y, Takekita Y, Mandelli L, Azuma J, Kinoshita T (2008) ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32:398-404
38. Vidal R, Pilar-Cuéllar F, dos Anjos S, Linge R, Treceño B, Vargas VI, Rodriguez-Gaztelumendi A, Mostany R, Castro E, Diaz A, Valdizán EM, Pazos A (2011) New strategies in the development of antidepressants: towards the modulation of neuroplasticity pathways. Curr Pharm Des 17:521-533
39. Maron E, Tammiste A, Kallassalu K, Eller T, Vasar V, Nutt DJ, Metspalu A (2009) Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression. Eur Neuropsychopharmacol 19:451-456
40. Serretti A, Kato M, De Ronchi D, 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 12:247-257
41. 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 61:1163-1169
42. Yoshida K, Takahashi H, Higuchi H, Kamata M, Ito K, Sato K, Naito S, Shimizu T, Itoh K, Inoue K, Suzuki T, Nemeroff CB (2004) Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms. Am J Psychiatry 161:1575-1580
43. 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 296:1609-1618
44. Higuchi H (2010) Prediction of antidepressant response to milnacipran and fluvoxamine using pharmacogenetical methods. Nihon Shinkei Seishin Yakurigaku Zasshi 30:71-76
45. Min W, Li T, Ma X, Li Z, Yu T, Gao D, Zhang B, Yun Y, Sun X (2009) Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response. Psychopharmacology 205:409-417
46. Dong C, Wong ML, Licinio J (2009) Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans. Mol Psychiatry 14:1105-1118
47. Tzeng DS, Chien CC, Lung FW, Yang CY (2009) MAOA gene polymorphisms and response to mirtazapine in major depression. Hum Psychopharmacol 24:293-300
48. Lung FW, Tzeng DS, Huang MF, Lee MB (2011) Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder. BMC Med Genet 12:74
49. Lemonde S, Du L, Bakish D, Hrdina P, Albert PR (2004) Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response. Int J Neuropsychopharmacol 7:501-506
50. Kato M, Fukuda T, Wakeno M, Okugawa G, Takekita Y, Watanabe S, Yamashita M, Hosoi Y, Azuma J, Kinoshita T, Serretti A (2009) Effect of 5-HT1A gene polymorphisms on antidepressant response in major depressive disorder. Am J Med Genet B Neuropsychiatr Genet 150B:115-123
51. Choi MJ, Kang RH, Ham BJ, Jeong HY, Lee MS (2005) Serotonin receptor 2A gene polymorphism (-1438A/G) and short-term treatment response to citalopram. Neuropsychobiology 52:155-162
52. Kato M, Fukuda T, Wakeno M, Fukuda K, Okugawa G, Ikenaga Y, Yamashita M, Takekita Y, Nobuhara K, Azuma J, Kinoshita T (2006) Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients. Neuropsychobiology 53:186-195
53. Minov C, Baghai TC, Schüle C, Zwanzger P, Schwarz MJ, Zill P, Rupprecht R, Bondy B (2001) Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression. Neurosci Lett 303:119-122
54. Lee SH, Lee KJ, Lee HJ, Ham BJ, Ryu SH, Lee MS (2005) Association between the 5-HT6 receptor C267T polymorphism and response to antidepressant treatment in major depressive disorder. Psychiatry Clin Neurosci 59:140-145
55. Illi A, Setälä-Soikkeli E, Viikki M, Poutanen O, Huhtala H, Mononen N, Lehtimäki T, Leinonen E, Kampman O (2009) 5-HTR1A, 5-HTR2A, 5-HTR6, TPH1 and TPH2 polymorphisms and major depression. NeuroReport 20:1125-1128
56. Perroud N, Aitchison KJ, Uher R, Smith R, Huezo-Diaz P, Marusic A, Maier W, Mors O, Placentino A, Henigsberg N, Rietschel M, Hauser J, Souery D, Kapelski P, Bonvicini C, Zobel A, Jorgensen L, Petrovic A, Kalember P, Schulze TG, Gupta B, Gray J, Lewis CM, Farmer AE, McGuffin P, Craig I (2009) Genetic predictors of increase in suicidal ideation during antidepressant treatment in the GENDEP project. Neuropsychopharmacology 34:2517-2528
57. Wakeno M, Kato M, Okugawa G, Fukuda T, Hosoi Y, Takekita Y, Yamashita M, Nonen S, Azuma J, Kinoshita T (2008) The alpha 2A-adrenergic receptor gene polymorphism modifies antidepressant responses to milnacipran. J Clin Psychopharmacol 28:518-524
58. Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ (2007) Genetic markers of suicidal ideation emerging during citalopram treatment of major depression. Am J Psychiatry 164:1530-1538
59. Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ, 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 164:1181-1188
60. Horstmann S, Lucae S, Menke A, Hennings JM, Ising M, Roeske D, Müller-Myhsok B, Holsboer F, Binder EB (2010) Polymorphisms in GRIK4, HTR2A, and FKBP5 show interactive effects in predicting remission to antidepressant treatment. Neuropsychopharmacology 35:727-740
61. 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 59:681-688
62. Wu GS, Luo HR, Dong C, Mastronardi C, Licinio J, Wong ML (2011) Sequence polymorphisms of MC1R gene and their association with depression and antidepressant response. Psychiatr Genet 21:14-18
63. 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 414:155-158
64. 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 9:1075-1082
65. Papiol S, Arias B, Gastó C, Gutiérrez B, Catalán R, Fañanás L (2007) Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment. J Affect Disord 104:83-90
66. Lin E, Chen PS, Chang HH, Gean PW, Tsai HC, Yang YK, Lu RB (2009) Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 33:1167-1172
67. Keers R, Bonvicini C, Scassellati C, Uher R, Placentino A, Giovannini C, Rietschel M, Henigsberg N, Kozel D, Mors O, Maier W, Hauser J, Souery D, Mendlewicz J, Schmäl C, Zobel A, Larsen ER, Szczepankiewicz A, Kovacic Z, Elkin A, Craig I, McGuffin P, Farmer AE, Aitchison KJ, Gennarelli M (2011) Variation in GNB3 predicts response and adverse reactions to antidepressants. J Psychopharmacol 25:867-874
68. Lekman M, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ, 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 63:1103-1110
69. Appel K, Schwahn C, Mahler J, Schulz A, Spitzer C, Fenske K, Stender J, Barnow S, John U, Teumer A, Biffar R, Nauck M, Völzke H, Freyberger HJ, Grabe HJ (2011) Moderation of adult depression by a polymorphism in the FKBP5 gene and childhood physical abuse in the general population. Neuropsychopharmacology 36:1982-1991
70. Zou YF, Wang Y, Liu P, Feng XL, Wang BY, Zang TH, Yu X, Wei J, Liu ZC, Liu Y, Tao M, Li HC, Li KQ, Hu J, Li M, Zhang KR, Ye DQ, Xu XP (2010) Association of brain-derived neurotrophic factor genetic Val66Met polymorphism with severity of depression, efficacy of fluoxetine and its side effects in Chinese major depressive patients. Int J Neuropsychopharmacol 13:93-101
71. Domschke K, Lawford B, Laje G, Berger K, Young R, Morris P, Deckert J, Arolt V, McMahon FJ, Baune BT (2010) Brain-derived neurotrophic factor (BDNF) gene: no major impact on antidepressant treatment response. Neuropsychobiology 61:71-78
72. Kocabas NA, Antonijevic I, Faghel C, Forray C, Kasper S, Lecrubier Y, Linotte S, Massat I, Mendlewicz J, Noro M, Montgomery S, Oswald P, Snyder L, Zohar J, Souery D (2011) Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder. Int Clin Psychopharmacol 26:1-10
73. Licinio J, Dong C, Wong ML (2009) Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response. Arch Gen Psychiatry 66:488-497
74. Heils A, Mossner R, Lesch KP (1997) The human serotonin transporter gene polymorphism - basic research and clinical implications. J Neural Transm 104:1005-1014
75. Taylor MJ, Sen S, Bhagwagar Z (2010) Antidepressant response and the serotonin transporter gene-linked polymorphic region. Biol Psychiatry 68:536-543
76. Mrazek DA, Rush AJ, Biernacka JM, O'Kane DJ, Cunningham JM, Wieben ED, Schaid DJ, Drews MS, Courson VL, Snyder KA, Black JL 3rd, Weinshilboum RM (2009) SLC6A4 variation and citalopram response. Am J Med Genet B Neuropsychiatr Genet 150B:341-351
77. Hu XZ, Rush AJ, Charney D, Wilson AF, Sorant AJ, Papanicolaou 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 64:783-792
78. Smeraldi E, Serretti A, Artioli P, Lorenzi C, Catalano M (2006) Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants. Psychiatr Genet 16:153-158
79. Baffa A, Hohoff C, Baune BT, Muller-Tidow C, Tidow N, Freitag C, Zwanzger P, Deckert J, Arolt V, Domschke K (2010) Norepinephrine and serotonin transporter genes: impact on treatment response in depression. Neuropsychobiology 62:121-131
80. Bonvicini C, Minelli A, Scassellati C, Bortolomasi M, Segala M, Sartori R, Giacopuzzi M, Gennarelli M (2010) Serotonin transporter gene polymorphisms and treatment-resistant depression. Prog Neuropsychopharmacol Biol Psychiatry 34:934-939
81. Uher R, Perroud N, Ng MY, Hauser J, Henigsberg N, Maier W, Mors O, Placentino A, Rietschel M, Souery D, Zagar T, Czerski PM, Jerman B, Larsen ER, Schulze TG, Zobel A, Cohen-Woods S, Pirlo K, Butler AW, Muglia P, Barnes MR, Lathrop M, Farmer A, Breen G, Aitchison KJ, Craig I, Lewis CM, McGuffin P (2010) Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. Am J Psychiatry 167:555-564
82. Molteni R, Cattaneo A, Calabrese F, Macchi F, Olivier JD, Racagni G, Ellenbroek BA, Gennarelli M, Riva MA (2010) Reduced function of the serotonin transporter is associated with decreased expression of BDNF in rodents as well as in humans. Neurobiol Dis 37:747-755
83. Calabrese F, Molteni R, Cattaneo A, Macchi F, Racagni G, Gennarelli M, Ellenbroek BA, Riva MA (2010) Long-term duloxetine treatment normalizes altered brain-derived neurotrophic factor expression in serotonin transporter knockout rats through the modulation of specific neurotrophin isoforms. Mol Pharmacol 77:846-853
84. Ham BJ, Lee BC, Paik JW, Kang RH, Choi MJ, Choi IG, Lee MS (2007) Association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population. Prog Neuropsychopharmacol Biol Psychiatry 31:104-107
85. Kato M, Wakeno M, Okugawa G, Fukuda T, Azuma J, Kinoshita T, Serretti A (2007) No association of TPH1 218A/C polymorphism with treatment response and intolerance to SSRIs in Japanese patients with major depression. Neuropsychobiology 56:167-171
86. Secher A, Bukh J, Bock C, Koefoed P, Rasmussen HB, Werge T, Kessing LV, Mellerup E (2009) Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1. Int Clin Psychopharmacol 24:199-203
87. Peters EJ, Slager SL, McGrath PJ, Knowles JA, Hamilton SP (2004) Investigation of serotonin-related genes in antidepressant response. Mol Psychiatry 9:879-889
88. Peters EJ, Slager SL, Jenkins GD, Reinalda MS, Garriock HA, Shyn SI, Kraft JB, McGrath PJ, Hamilton SP (2009) Resequencing of serotonin-related genes and association of tagging SNPs to citalopram response. Pharmacogenet Genomics 19:1-10
89. Teicher MH, Glod CA, Cole JO (1993) Antidepressant drugs and the emergence of suicidal tendencies. Drug Saf 8:186-212
90. Healy D, Whitaker C (2003) Antidepressants and suicide: risk-benefit conundrums. J Psychiatry Neurosci 28:331-337
91. Olfson M, Marcus SC, Shaffer D (2006) Antidepressant drug therapy and suicide in severely depressed children and adults: a case-control study. Arch Gen Psychiatry 63:865-872
92. Laje G, Perlis RH, Rush AJ, McMahon FJ (2009) Pharmacogenetics studies in STAR*D: strengths, limitations, and results. Psychiatr Serv 60:1446-1457
93. Dowlatshahi D, MacQueen GM, Wang JF, Young LT (1998) Increased temporal cortex CREB concentrations and antidepressant treatment in major depression. Lancet 352:1754-1755
94. Dwivedi Y, Rao JS, Rizavi HS, Kotowski J, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects. Arch Gen Psychiatry 60:273-282
95. Young LG, Bezchlibnyk YB, Chen B, Wang JF, MacQueen GM (2004) Amygdala cyclic adenosine monophosphate response element binding protein phosphorylation in patients with mood disorders: effects of diagnosis, suicide and drug treatment. Biol Psychiatry 55:570-577
96. Perlis RH, Purcell S, Fava M, Fagerness J, Rush AJ, Trivedi MH, Smoller JW (2007) Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element bind protein in the STAR*D study. Arch Gen Psychiatry 64:689-697
97. Dwivedi Y (2009) Brain-derived neurotrophic factor: role in depression and suicide. Neuropsychiatr Disord Treat 5(433):449
98. Sairanen M, O'Leary OF, Knuuttila JE, Castren E (2007) Chronic antidepressant treatment selectively increases expression of plasticity related proteins in the hippocampus and medial prefrontal cortex of the rat. Neuroscience 144:368-374
99. Martinowich K, Manji H, Lu B (2007) New insights into BDNF function in depression and anxiety. Nat Neurosci 10:1089-1093
100. Bueller JA, Aftab M, Sen S, Gomez-Hassan D, Burmeister M, Zubieta JK (2006) BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biol Psychiatry 59:812-815
101. Sarchiapone M, Carli V, Roy A, Iacoviello L, Cuomo C, Latella MC, di Giannantonio M, Janiri L, de Gaetano M, Janal MN (2008) Association of polymorphism (Val66Met) of brain-derived neurotrophic factor with suicide attempts in depressed patients. Neuropsychobiology 57:139-145
102. Henningsson S, Borg J, Lundberg J, Bah J, Lindström M, Ryding E, Jovanovic H, Saijo T, Inoue M, Rosén I, Träskman-Bendz L, Farde L, Eriksson E (2009) Genetic variation in brain-derived neurotrophic factor is associated with serotonin transporter but not serotonin-1A receptor availability in men. Biol Psychiatry 66:477-485
103. Kohli MA, Salyakina D, Pfennig A, Lucae S, Horstmann S, Menke A, Kloiber S, Hennings J, Bradley BB, Ressler KJ, Uhr M, Müller-Myhsok B, Holsboer F, Binder EB (2010) Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients. Arch Gen Psychiatry 67:348-359
104. Cheng R, Juo SH, Loth JE, Nee J, Iossifov I, Blumenthal R, Sharpe L, Kanyas K, Lerer B, Lilliston B, Smith M, Trautman K, Gilliam TC, Endicott J, Baron M (2006) Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder. Mol Psychiatry 11:252-260
105. Wochnik GM, Rüegg J, Abel GA, Schmidt U, Holsboer F, Rein T (2005) FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 280:4609-4616
106. Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Pütz B, Papiol S, Seaman S, Lucae S, Kohli MA, Nickel T, Künzel 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, Köhnlein O, Dabitz H, Brückl T, Müller N, Pfister H, Lieb R, Mueller JC, Lõhmussaar 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 36:1319-1325
107. Roy A, Gorodetsky E, Yuan Q, Goldman D, Enoch MA (2010) Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology 35:1674-1683
108. Palucha A, Pilc A (2005) The involvement of glutamate in the pathophysiology of depression. Drug News Perspect 18:262-268
109. Sequeira A, Mamdani F, Ernst C, Vawter MP, Bunney WE, Lebel V, Rehal S, Klempan T, Gratton A, Benkelfat C, Rouleau GA, Mechawar N, Turecki G (2009) Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS ONE 4:e6585
110. Price RB, Nock MK, Charney DS, Mathew SJ (2009) Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 66:522-526
111. Smits KM, Smits LJ, Schouten JS, Stelma FF, Nelemans P, Prins MH (2004) Influence of SERTPR and STin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic review. Mol Psychiatry 9:433-441
112. de Leon J (2007) The crucial role of the therapeutic window in understanding the clinical relevance of the poor versus the ultrarapid metabolizer phenotypes in subjects taking drugs metabolized by CYP2D6 or CYP2C19. J Clin Psychopharmacol 27:241-245
113. DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr (2010) Rapid resolution of suicidal ideation after a single infusion of an N-methyl-d-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry 71:1605-1611
114. Karr JR, Sanghvi JC, Macklin DN, Gutschow MV, Jacobs JM, Bolival B Jr, Assad-Garcia N, Glass JI, Covert MW (2012) A whole-cell computational model predicts phenotype from genotype. Cell 150:389-401
115. Desta Z, Zhao X, Shin JG, Flockhart DA (2002) Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 41:913-958