Pharmacogenetics of risperidone response and induced side effects

Personalized Medicine

Volumn 4, Issue 3, 2007, Pages 271-293

  Correia, Catarina ^a,b   Vicente, Astrid M ^a,b  

^a INSTITUTO GULBENKIAN DE CIÊNCIA   (Portugal)

^b NATIONAL INSTITUTE OF HEALTH DR RICARDO JORGE   (Portugal)

Author keywords

Antipsychotics; Hyperprolactinemia; Pharmacodynamics; Pharmacogenetics; Pharmacokinetics; Risperidone; Weight gain

Indexed keywords

AMISULPRIDE; ANTIARRHYTHMIC AGENT; ANTIDEPRESSANT AGENT; ATYPICAL ANTIPSYCHOTIC AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CHLORPROMAZINE; CLOZAPINE; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE 4 RECEPTOR; FLUPENTIXOL; FLUPHENAZINE DECANOATE; HALOPERIDOL; HALOPERIDOL DECANOATE; MULTIDRUG RESISTANCE PROTEIN 1; NEUROLEPTIC AGENT; OLANZAPINE; OPIATE; PALIPERIDONE; QUETIAPINE; RISPERIDONE; SEROTONIN 2A RECEPTOR; SEROTONIN 6 RECEPTOR; SEROTONIN UPTAKE INHIBITOR; SULPIRIDE; THIORIDAZINE; ZUCLOPENTHIXOL;

AKATHISIA; AUTISM; AUTOMUTILATION; BIPOLAR DISORDER; BRIEF PSYCHOTIC DISORDER; CHROMOSOME 13Q; CHROMOSOME 22Q; CHROMOSOME 7Q; CLINICAL TRIAL; DELUSIONAL DISORDER; DEPRESSION; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG RESPONSE; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSTONIA; EXTRAPYRAMIDAL SYMPTOM; GALACTORRHEA; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC RISK; GENETIC VARIABILITY; GROWTH DISORDER; GYNECOMASTIA; HIRSUTISM; HUMAN; HYPERACTIVITY; HYPERPROLACTINEMIA; INFERTILITY; LIPID BLOOD LEVEL; LONG QT SYNDROME; MAJOR DEPRESSION; MANIA; MENSTRUATION DISORDER; MENTAL DEFICIENCY; MOOD DISORDER; MOTOR DYSFUNCTION; ORTHOSTATIC HYPOTENSION; OSTEOPENIA; PARKINSONISM; PATIENT COMPLIANCE; PHARMACODYNAMICS; PHARMACOGENETICS; PHENOTYPE; PRIORITY JOURNAL; PROLACTIN BLOOD LEVEL; PSYCHOSIS; RECEPTOR AFFINITY; RECEPTOR BLOCKING; REVIEW; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; SEDATION; SEXUAL DYSFUNCTION; SEXUAL MATURATION; SIDE EFFECT; TARDIVE DYSKINESIA; WEIGHT GAIN; XEROSTOMIA;

EID: 34548453957     PISSN: 17410541     EISSN: 1744828X     Source Type: Journal    
DOI: 10.2217/17410541.4.3.271     Document Type: Review

References (128)

1. Gardner DM, Baidessarini RJ, Waraich P: Modern antipsychotic drugs: a critical overview. CMAJ 172(13), 1703-1711 (2005).
2. Freudenreich O, Goff DC: Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current combinations. Acta Psychiatr. Scand. 106(5), 323-330 (2002).
3. de Leon J, Armstrong SC, Cozza KL.: The dosing of atypical antipsychotics. Psychosomatics 46(3), 262-273 (2005).
4. Spina E, de Leon J: Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin. Pharmacol. Toxicol. 100(1), 4-22 (2007).
5. Malhotra AK: Candidate gene studies of antipsychotic drug efficacy and drug-induced weight gain. Neurotox. Res. 6(1), 51-56 (2004a).
6. Moller HJ: Risperidone: a review. Expert Opin. Pharmacother. 6(5), 803-818 (2005).
7. Farah A: Atypicality of atypical antipsychotics. Prim. Care Companion J. Clin. Psychiatry 7 (6), 268-274 (2005).
8. Lieberman JA, Stroup TS, McEvoy JP et al.; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353(12), 1209-1223 (2005).
9. Jones HM, Pilowsky LS: Dopamine and antipsychotic drug action revisited. Br. J. Psychiatry 181, 271-275 (2002).
10. Meltzer HY, Li Z, Kaneda Y, Ichikawa J: Serotonin receptors: their key role in drugs to treat schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 27(7), 1159-1172 (2003).
11. Seeman P: Atypical antipsychotics: mechanism of action. Can. J. Psychiatry 47(1), 27-38 (2002).
12. Svensson TH: α-adrenoceptor modulation hypothesis of antipsychotic atypicality. Prog. Neuropsychopharmacol. Biol. Psychiatry 27(7), 1145-1158 (2003).
13. de Deyn PP, Buitelaar J: Risperidone in the management of agitation and aggression associated with psychiatric disorders. Eur. Psychiatry 21(1), 1-8 (2006).
14. Nemeroff CB: Use of atypical antipsychotics in refractory depression and anxiety. J. Clin. Psychiatry 66(Suppl. 8), 13-21 (2005)
15. Chavez B, Chavez-Brown M, Rey JA: Role of risperidone in children with autism spectrum disorder. Ann. Pharmacother. 40(5), 909-916 (2006).
16. Pandina GJ, Aman MG, Findling RL: Risperidone in the management of disruptive behavior disorders. J. Child Adolesc. Psychopharmacol. 16(4), 379-392 (2006)
17. West L, Waldrop J: Risperidone use in the treatment of behavioral symptoms in children with autism. Pediatr. Nurs. 32(6), 545-549 (2006).
18. Yasui-Furukori N, Kondo T, Suzuki A, Mihara K, Kaneko S: Comparison of prolactin concentrations between haloperidol and risperidone treatments in the same female patients with schizophrenia. Psychopharmacology 162(1), 63-66 (2002).
19. Melkersson K: Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J. Clin. Psychiatry 66(6), 761-767 (2005).
20. Wieck A, Haddad PM: Antipsychotic-induced hyperprolactinaemia in women: pathophysiology, severity and consequences. Br. J. Psyshiatry 182, 199-204 (2003).
21. Naidoo U, Goff DC, Klibanski A: Hyperprolactinemia and bone mineral density: the potential impact of antipsychotic agents. Psychoneuroendocrinology 28(Suppl. 2), 97-108 (2003).
22. Findling RL, Kusumakar V, Daneman D, Moshang T, de Smedt G, Binder C: Prolactin levels during long-term risperidone treatment in children and adolescents. J. Clin. Psychiatry 64, 1362-1369 (2003).
23. Anderson GM, Scahill L, McCracken JT et al.: Effects of short- and long-term risperidone treatment on prolactin levels in children with autism. Biol. Psyschiatry 61(4), 545-550 (2007).
24. Kinon BJ, Gilmore JA, Liu H, Halbreich UM: Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology 28(Suppl. 2), 55-68 (2003).
25. Kapur S, Langlois X, Vinken P, Megens AA, de Coster R, Andrews JS: The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats. J. Pharmacol. Exp.. Ther. 302(3), 1129-1134 (2002)
26. Tauscher J, Jones C, Remington G, Zipursky RB, Kapur S: Significant dissociation of brain and plasma kinetics with antipsychotics. Mol. Psychiatry 7(3), 317-321 (2002).
27. Gentile S: Long-term treatment with atypical antipsychotics and the risk of weight gain: a literature analysis. Drug Saf. 29(4), 303-319 (2006)
28. Melkersson K, Dahl ML: Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs 64(7), 701-723 (2004)
29. Allison DB, Casey DE: Antipsychotic-induced weight gain: a review of the literature. J. Clin. Psychiatry 62 (Suppl. 7) 22-31 (2001)
30. Theisen FM, Gebhardt S, Haberhausen M et al.: Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs. Psychiatr. Genet. 15(4), 285-289 (2005).
31. Wehmeier PM, Gebhardt S, Schmidtke J, Remschmidt H, Hebebrand J, Theisen FM: Clozapine: weight gain in a pair of monozygotic twins concordant for schizophrenia and mild mental retardation. Psychiatry Res. 133(2-3), 273-276 (2005)
32. Heykants J, Huang ML, Mannens G et al.: The pharmacokinetics of risperidone in humans: a summary. J. Clin. Psychiatry 55(Suppl.), 13-17 (1994).
33. Boulton DW, De Vane CL, Liston HL, Markowitz JS: In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 71(2), 163-169 (2002).
34. Mannens G, Meuldermans W. Snoeck E, Heykants J: Plasma protein binding of risperidone and its distribution in blood. Psychopharmacology 114(4), 566-572 (1994).
35. Bork JA, Rogers T, Wedlund PJ, de Leon J: A pilot study on risperidone metabolism: the role of cytochromes P450 2D6 and 3A. J. Clin. Psychiatry 60(7), 469-476 (1999).
36. Yasui-Furukori N, Hidestrand M, Spina E, Facciola G, Scordo MG, Tybring G: Different enantioselective 9-hydroxylation of risperidone by the two human CYP2D6 nd CYP3A4 enzymes. Drug Metab. Dispos. 29(10), 1263-1268 (2001).
37. Yasui-Furukori N, Mihara K, Kondo T et al.: Effects of CYP2D6 genotypes on plasma concentrations of risperidone and enantiomers of 9-hydroxyrisperidone in Japanese patients with schizophrenia. J. Clin. Pharmacol. 43(2), 122-127 (2003).
38. van Beijsterveldt LE, Geerts RJ, Leysen JE et al.: Regional brain distribution of risperidone and its active metabolite 9-hydroxy-risperidone in the rat. Psychopharmacology 114(1), 53-62 (1994).
39. Wang JS, Ruan Y, Taylor RM, Donavan JL Markowitz JS, DeVane CL: The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein. Int. J. Neuropsychopharmacol. 7(4), 415-419 (2004).
40. Balant-Gorgia AE, Gex-Fabry M, Genet C. Balant LP: Therapeutic drug monitoring of risperidone using a new, rapid HPLC method: reappraisal of interindividual variability factors. Ther. Drug Monit. 21(1). 105-115 (1999).
41. Ingelman-Sundberg M: Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol. Sci. 25(4), 193-200 (2004).
42. Ingelman-Sundberg M: Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn Schmiedebergs Arch. Pharmacol. 369(1), 89-104 (2004b).
43. Ingelman-Sundberg M: The human genome project and novel aspects of cytochrome P450 research. Toxicol. Appl. Pharmacol. 207(2 Suppl), 52-56 (2005).
44. Daly AK: Pharmacogenetics of the cytochromes P450. Curr. Top. Med. Chem. 4(16), 1733-1744 (2004).
45. Bertilsson L, Dahl ML, Dalen P, Al-Shurbaji A: Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br. J. Clin. Pharmacol. 53(2), 111-122 (2002).
46. Sabbagh A, Darlu P: Data-mining methods as useful tools for predicting individual drug response: application to CYP2D6 data. Hum. Hered. 62(3), 119-134 (2006)
47. Cascorbi I. Pharmacogenetics of cytochrome p4502D6: genetic background and clinical implication. Eur. J. Clin. Invest. 33(Suppl. 2), 17-22 (2003).
48. Raimundo S, Toscano C, Klein K: A novel intronic mutation, 2988G>A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects. Clin. Pharmacol. Ther. 76(2), 128-138 (2004).
49. Scordo MG, Spina E, Facciola G, Avenoso A, Johansson I, Dahl ML: Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology 147(3), 300-305 (1999).
50. Berecz R, LLerena A, de la Ruble A et al.: Relationship between risperidone and 9-hydroxy-risperidone plasma concentrations and CYP2D6 enzyme activity in psychiatric patients. Pharmacopsychiatry 35(6), 231-234 (2002).
51. Nyberg S, Dahl ML, Handin C: A PET study of D2 and 5-HT2 receptor occupancy induced by risperidone in poor metabolizers of debrisoquin and risperidone. Psychopharmacology 119, 345-348 (1995).
52. Mihara K, Kondo T, Yasui-Furukori N et al.: Effects of various CYP2D6 genotypes on the steady-state plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, in Japanese patients with schizophrenia. Ther. Drug Monit. 25(3), 287-293 (2003).
53. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 68(1), 29-39 (2000).
54. Kirchheiner J, Nickchen K, Bauer M et al.: Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol. Psychiatry 9(5), 442-473 (2004).
55. Andreassen OA. MacEwan T, Gulbrandsen AK, McCreadie RG. Steen VM: Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients. Psychopharmacology 131(2), 174-179 (1997).
56. de Leon J, Barnhill J, Rogers T, Boyle J, Chou WH, Wedlund PJ: Pilot study of the cytochrome P450-2D6 genotype in a psychiatric state hospital. Am. J. Psychiatry 155 (9), 1278-1280 (1998).
57. Kohnke MD, Griese EU, Stosser D, Gaertner I, Barth G: Cytochrome P450 2D6 deficiency and its clinical relevance in a patient treated with risperidone. Pharmacopsychiatry 35(3), 116-118 (2002)
58. Chou WH, Yan FX, de Leon J et al.: Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness. J. Clin. Psychopharmacol. 20(2), 246-251 (2000).
59. Llerena A, Berecz R, Dorado P, de la Rubia A: QTc interval, CYP2D6 and CYP2C9 genotypes and risperidone plasma concentrations. J. Psychopharmacol. 18 (2), 189-193 (2004).
60. Prior TI, Baker GB: Interactions between the cytochrome P450 system and the second-generation antipsychotics. J. Psychiatry Neurosci. 28(2), 99-112 (2003).
61. de Leon J, Susce MT, Pan RM, Fairchild M, Koch WH, Wedlund PJ: The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J. Clin. Psychiatry 66(1), 15-27 (2005).
62. de Leon J, Susce MT, Pan RM, Koch WH, Wedlund PJ: Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. J. Clin. Psychopharmacol. 25(5), 448-456 (2005).
63. Plesnicar BK, Zalar B, Breskvar K, Dolzan V: The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment. J. Psychopharmacol. 20(6), 829-833 (2006)
64. Lane HY, Liu YC, Huang CL et al.: Risperidone-related weight gain: genetic and nongenetic predictors. J. Clin. Psychopharmacol. 26(2), 128-134 (2006).
65. Troost PW, Lahuis BE, Hermans MH et al.: Prolactin release in children treated with risperidone: impact and role of CYP2D6 metabolism. J. Clin. Psychopharmacol. 27(1), 52-57 (2007).
66. Knegtering R, Baselmans P, Castelein S, Bosker F, Bruggeman R, van den Bosch RJ: Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels. Am. J. Psychiatry 162, 1010-1012 (2005).
67. Melkersson KI: Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite. Hum. Psychopharmacol. 21(8), 529-532 (2006).
68. Kakihara S, Yoshimura R, Shinkai K et al.: Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6. Int. Clin. Psychopharmacol. 20(2), 71-78 (2005).
69. Riedel M, Schwarz MJ, Strassnig M et al.: Risperidone plasma levels, clinical response and side-effects. Eur. Arch. Psychiatry Clin. Neurosci. 255(4), 261-268 (2005).
70. Schwab M, Eichelbaum M, Fromm MF: Genetic polymorphisms of the human MDR1 drug transporter. Annu. Rev. Pharmacol. Toxicol. 43, 285-307 (2003).
71. Kurata Y, Ieiri I, Kimura M et al.: Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin. Pharmacol. Ther. 72(2), 209-219 (2002).
72. Johne A, Kopke K, Gerloff T et al.: Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin. Pharmacol. Ther. 72(5), 584-594 (2002).
73. Chowbay B, Cumaraswamy S, Cheung YB, Zhou Q, Lee EJ: Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients. Pharmacogenetics 13(2), 89-95 (2003).
74. Yi SY, Hong KS, Lim HS et al.: A variant 2677A allele of the MDR1 gene affects fexofenadine disposition. Clin. Pharmacol. Ther. 76(5), 418-427 (2004).
75. Tanabe M, Ieiri I, Nagata N et al.: Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J. Pharmacol. Exp. Ther. 297(3), 1137-1143 (2001).
76. Taniguchi S, Mochida Y, Uchiumi T et al.: Genetic polymorphism at the 5′ regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon. Mol. Cancer Ther. 2(12), 1351-1359 (2003).
77. Yasui-Furukori N, Mihara K, Takahata T et al.: Effects of various factors on steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone: lack of impact of MDR-1 genotypes. Br. J. Clin. Pharmacol. 57(5), 569-575 (2004).
78. Xing Q, Gao R, Li H et al.: Polymorphisms of the ABCB1 gene are associated with the therapeutic response to risperidone in Chinese schizophrenia patients. Pharmacogenomics 7(7), 987-993 (2006).
79. Arnt J, Skarsfeldt T: Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology, 18(2), 63-101(1998).
80. Schotte A, Janssen PF, Gommeren W et al.: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology 124(1-2), 57-73 (1996).
81. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J. Clin. Psychiatry 55(Suppl.), 5-12 (1994)
82. Kondo T, Mihara K, Suzuki A, Yasui-Furukori N, Kaneko S: Combination of dopamine D2 receptor gene polymorphisms as a possible predictor of treatment-resistance to dopamine antagonists in schizophrenic patients. Prog. Neuropsychopharmacol. Biol. Psychiatry 27(6), 921-926 (2003).
83. Lencz T, Robinson DG, Xu K et al.: DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am. J. Psychiatry 163(3), 529-531 (2006).
84. Xing Q, Qian X, Li H et al.: The relationship between the therapeutic response to risperidone and the dopamine D2 receptor polymorphism in Chinese schizophrenia patients. Int. J. Neuropsychopharmacol. 1-7 (2006).
85. Laakso A, Pohjalainen T, Bergman J et al.: The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal L-amino acid decarboxylase in healthy subjects. Pharmacogenet. Genomics 15(6), 387-391 (2005).
86. Dubertret C, Gouya L, Hanoun N et al.: The 3′ region of the DRD2 gene is involved in genetic susceptibility to schizophrenia. Schizophr. Res. 67, 75-85 (2004).
87. Neville MJ, Johnstone EC, Walton RT: Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum. Mutat. 23, 540-545 (2004).
88. Malhotra AK, Murphy GM Jr, Kennedy JL: Pharmacogenetics of psychotropic drug response. Am. J. Psychiatry 161(5), 780-796 (2004).
89. Yamanouchi Y, Iwata N, Suzuki T, Kitajima T, Ikeda M, Ozaki N: Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone. Pharmacogenomics J. 3, 356-361 (2003).
90. Lane HY, Lee CC, Liu YC, Chang WH: Pharmacogenetic studies of response to risperidone and other newer atypical antipsychotics. Pharmacogenomics 6(2), 139-149 (2005).
91. Young RM, Lawford BR, Barnes M et al.: Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele. Br. J. Psychiatry 185, 147-151 (2004).
92. Duan J, Wainwright MS, Comeron JM et al.: Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum. Mol. Genet. 12, 205-216 (2003).
93. Hirvonen M, Laakso A, Nagren K, Rinne JO, Pohjalainen T, Hietala J: C957T polymorphism of the dopamine D2 receptor (DRD2) gene affects striatal DRD2 availability in vivo. Mol. Psychiatry 9. 1060-1061 (2004).
94. Lane HY, Lee CC, Chang YC, Lu CT, Huang CH, Chang WH: Effects of dopamine D2 receptor Ser311Cys polymorphism and clinical factors on risperidone efficacy for positive and negative symptoms and social function. Int. J. Neuropsychopharmacol. 7(4), 461-470 (2004).
95. Wong AH, Buckle CE, van Tol HH: Polymorphisms in dopamine receptors: what do they tell us? Eur. J. Pharmacol. 410(2-3), 183-203 (2000).
96. Lerer B, Segman RH, Fangerau H et al.: Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism. Neuropsychopharmacology 27(1), 105-119 (2002).
97. Szekeres G, Kerl S, Juhasz A et al.: Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia. Am. J. Med. Genet. B Neuropsychiatr. Genet. 124(1), 1-5 (2004).
98. Lane HY, Hsu SK, Liu YC, Chang YC, Huang CH, Chang WH: Dopamine D3 receptor Ser9Gly polymorphism and risperidone response. J. Clin. Pychopharmacol. 25(1), 6-11 (2005).
99. Reynolds GP, Yao Z, Zhang X, Sun J, Zhang Z: Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response. Eur. Neuropsychopharmacol. 15(2), 143-151 (2005).
100. Zalsman G, Frisch A, Lev-Ran S et al.: DRD4 exon III polymorphism, and response risperidone in Israeli adolescents with schizophrenia: a pilot pharmacogenetic study. Eur. Neuropsychopharmacol. 13(3), 183-185 (2003).
101. Lane HY, Chang YC, Chiu CC, Chen ML, Hsieh MH, Chang WH: Association of risperidone treatment response with a polymorphism in the 5-HT(2A) receptor gene. Am. J. Psychiatry 159, 1593-1595 (2002).
102. Polesskaya OO, Sokolov BP: Differential expression of the "C" and "T" alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J. Neurosci. Res. 67(6), 812-822 (2002).
103. Mou XD, Zhang ZJ, Yao ZJ et al.: No association of-1438G/A polymorphism in promoter region of 5-HT2A receptor gene with antipsychotic agent-induced weight gain. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 22(5), 575-576 (2005).
104. Ozaki N, Manji H, Lubierman V et al.: A naturally occurring amino acid substitution of the human serotonin 5-HT2A receptor influences amplitude and timing of intracellular calcium mobilization. J. Neurochem. 68, 2186-2193 (1997).
105. Veenstra-VanderWeele J, Anderson GM, Cook EH Jr: Pharmacogenetics and the serotonin system: initial studies and future directions. Eur. J. Pharmacol. 410(2-3), 165-181 (2000).
106. di Matteo V, Cacchio, M, di Giulio C, Esposito E: Role of serotonin(2C) receptors in the control of brain dopaminergic function. Pharmacol. Biochem. Behav. 71(4), 727-734 (2002).
107. Basile VS, Masellis M, Potkin SG, Kennedy JL: Pharmacogenomics in schizophrenia: the quest for individualized therapy. Hum. Mol. Genet. 11(20), 2517-2530 (2002)
108. Reynolds GP, Zhang ZJ, Zhang XB: Association of antipsychotic drug-nduced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene. Lancet 359, 2086-2087 (2002).
109. Zhang Z, Zhang X, Yao Z et al.: Association of antipsychotic agent-induced weight gain with a polymorphism of the promoter region of the 5-HT2C receptor gene. Zhonghua Yi Xue Za Zhi 82(16), 1097-1101 (2002).
110. Ryu S, Cho EY, Park T et al.: 759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment. Prog. Neuropsychopharmacol. Biol. Psychiatry 31(3), 673-677 (2007).
111. Templeman LA, Reynolds GP, Arranz B, San L: Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet. Genomics 15(4), 195-200 (2005).
112. Yuan X, Yamada K, Ishiyama-Shigemoto S, Koyama W, Nonaka K: Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes. Diabetologia 43(3), 373-376 (2000).
113. Buckland PR, Hoogendoorn B, Guy CA, Smith SK, Coleman SL, O'Donovan MC: Low gene expression conferred by association of an allele of the 5-HT2C receptor gene with antipsychotic-induced weight gain. Am. J. Psychiatry 162 (3), 613-615 (2005).
114. Matsumoto M, Togashi H, Mori K, Ueno K, Miyamoto A, Yoshioka M: Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex. Eur. J. Pharmacol. 383(1), 39-48 (1999).
115. Pouzet B, Didriksen M, Arnt J: Effects of the 5-HT(6) receptor antagonist, SB-271046, in animal models for schizophrenia. Pharmacol. Biochem. Behav. 71(4), 635-643 (2002).
116. Lane HY, Lin CC, Huang CH, Chang YC, Hsu SK, Chang WH: Risperidone response and 5-HT6 receptor gene variance: genetic association analysis with adjustment for nongenetic confounders. Schizophr. Res. 67(1), 63-70 (2004).
117. Muller DJ, Klempan TA, de Luca V: The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neurosci. Lett. 379(2), 81-89 (2005).
118. Angelucci F, Mathe AA, Aloe L: Neurotrophic factors and CNS disorders: findings in rodent models of depression and schizophrenia. Prog. Brain Res. 146, 151-65 (2004).
119. Chlan-Fourney J, Ashe P, Nylen K, Juorio AV, Li XM: Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration. Brain Res. 954(1), 11-20 (2002).
120. Ribases M, Gratacos M, Armengol L et al.: Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associate with anorexia nervosa restrictive type. Mol. Psychiatry 8(8), 745-751 (2003).
121. Ribases M, Gratacos M, Fernandez-Aranda F et al.: Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations. Hum. Mol. Genet. 13(12), 1205-1212 (2004).
122. Lesch KP, Gutknecht L: Pharmacogenetics of the serotonin transporter. Prog. Neuropsychopharmacol. Biol. Psychiatry 29(6), 1062-1073 (2005).
123. Wang L, Yu L, He G et al.: Response of risperidone treatment may be associated with polymorphisms of HTT gene in Chinese schizophrenia patients. Neurosci. Lett. 414(1), 1-4 (2007).
124. Rudolf S, Peters M, Rothermundt M, Arolt V, Kirchner H: The influence of typical and atypical neuroleptic drugs in the production of interleukin-2 and interferon-γ in vitro. Neuropsychobiology 46(4), 180-185 (2002).
125. Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC: Changes in serum interieukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J. Clin. Psychiatry 65(7), 940-947 (2004).
126. Muller N, Riedel M, Scheppach C et al.: Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am. J. Psychiatry 159(6), 1029-1034 (2002).
127. Mata I, Crespo-Facorro B, Perez-Iglesias R et al.: Association between the interleukin-1 receptor antagonist gene and negative symptom improvement during antipsychotic treatment. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141(8), 939-943 (2006).
128. Arranz MJ, Munro J, Birkett J et al.: Pharmacogenetic prediction of clozapine response. Lancet 355(9215), 1615-1616 (2000).