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Human Physiology

, Volume 44, Issue 6, pp 706–719 | Cite as

Peculiarities of the Effect of Antipsychotics: Pharmacogenetic Studies

  • A. E. Gareeva
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  • 8 Downloads

Abstract

Currently, antipsychotics are the only type of drugs for the treatment of schizophrenia. The efficacy of antipsychotics in the treatment of schizophrenia is unsatisfactory. Specifically, more than 20% of schizophrenia patients are antipsychotic-resistant patients not sensitive to at least two antipsychotics. A combination of factors affecting the drug metabolism (pharmacokinetics) and the drug action (pharmacodynamics) underlies the differences in the response to the same antipsychotic agent. There is an obvious genetic contribution to the variability of response to psychotropic agents. Moreover, it is known that side effects caused by administration of these drugs may have an even stronger genetic component. This review presents the results of the most recent world research in the field of pharmacogenetics of antipsychotics.

Keywords:

schizophrenia pharmacogenetics antipsychotics 

Notes

REFERENCES

  1. 1.
    Tybura, P., Trześniowska-Drukała, B., Bienkowski, P., et al., Pharmacogenetics of adverse events in schizophrenia treatment: comparison study of ziprasidone, olanzapine and perazine, Psychiatry Res., 2014, vol. 219, no. 2, p. 261.CrossRefPubMedGoogle Scholar
  2. 2.
    Stroup, T.S., Lieberman, J.A., McEvoy, J.P., et al., Results of phase 3 of the CATIE schizophrenia trial, Schizophr. Res., 2009, vol. 107, no. 1, p. 1.CrossRefPubMedGoogle Scholar
  3. 3.
    Bakker, P.R., van Harten, P.N., and van Os, J., Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2, and MnSOD genes: a meta-analysis of pharmacogenetic interactions, Mol. Psychiatry, 2008, vol. 13, no. 5, p. 544.CrossRefPubMedGoogle Scholar
  4. 4.
    Potkin, S.G., Kimura, T., and Guarino, J., A 6-week, double-blind, placebo- and haloperidol-controlled, phase II study of lurasidone in patients with acute schizophrenia, Ther. Adv. Psychopharmacol., 2015, vol. 5, no. 6, p. 322.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yue, Y., Kong, L., Wang, J., et al., Regional abnormality of grey matter in schizophrenia: effect from the illness or treatment? PloS One, 2016, vol. 11, no. 1, p. e0147204.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sánchez, N., Coura, R., Engmann, O., et al., Haloperidol-induced Nur77 expression in striatopallidal neurons is under the control of protein phosphatase 1 regulation by DARPP-32, Neuropharmacology, 2014, vol. 79, p. 559.CrossRefPubMedGoogle Scholar
  7. 7.
    Pouget, J.G. and Müller, D.J., Pharmacogenetics of antipsychotic treatment in schizophrenia, Methods Mol Biol., 2014, vol. 1175, p. 557.CrossRefPubMedGoogle Scholar
  8. 8.
    Naumovska, Z., Nestorovska, A.K., Filipce, A., et al., Pharmacogenetics and antipsychotic treatment response, Prilozi, 2015, vol. 36, no. 1, p. 53.CrossRefPubMedGoogle Scholar
  9. 9.
    Xing, Q., Qian, X., Li, H., et al., The relationship between the therapeutic response to risperidone and dopamine D2 receptor polymorphism in Chinese schizophrenia patients, Int. J. Neuropsychopharmacol., 2007, vol. 10, no. 5, p. 631.CrossRefPubMedGoogle Scholar
  10. 10.
    Lencz, T., Robinson, D.G., Xu, K., et al., DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in the first-episode schizophrenia patients, Am. J. Psychiatry, 2006, vol. 163, no. 3, p. 529.CrossRefPubMedGoogle Scholar
  11. 11.
    Kang, S.G., Na, K.S., Lee, H.J., et al., DRD2 genotypic and haplotype variation is associated with improvements in negative symptoms after 6 weeks’ amisulpride treatment, J. Clin. Psychopharmacol., 2015, vol. 35, no. 2, p. 158.CrossRefPubMedGoogle Scholar
  12. 12.
    Giegling, I., Balzarro, B., Porcelli, S., et al., Influence of ANKK1 and DRD2 polymorphisms in response to haloperidol, Eur. Arch. Psychiatry Clin. Neurosci., 2013, vol. 263, no. 1, p. 65.CrossRefPubMedGoogle Scholar
  13. 13.
    Huang, L., Ohi, K., Chang, H., et al., A comprehensive meta-analysis of ZNF804A SNPs in the risk of schizophrenia among Asian populations, Am. J. Med. Genet., Part B, 2016, vol. 171, no. 3, p. 437.Google Scholar
  14. 14.
    Suzuki, M., Hurd, Y.L., Sokoloff, P., et al., D3 dopamine receptor mRNA is widely expressed in the human brain, Brain Res., 1998, vol. 779, no. 1, p. 58.CrossRefPubMedGoogle Scholar
  15. 15.
    Vehof, J., Burger, H., Wilffert, B., et al., Clinical response to antipsychotic drug treatment: association study of polymorphisms in six candidate genes, Eur. Neuropsychopharmacol., 2012, vol. 22, no. 9, p. 625.CrossRefPubMedGoogle Scholar
  16. 16.
    Xu, Q., Wu, X., Li, M., et al., Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population, Pharmacogenomics J., 2016, vol. 6, no. 4, p. 357.CrossRefGoogle Scholar
  17. 17.
    Bosia, M., Lorenzi, C., Pirovano, A., et al., COMT Val158Met and 5–HT1A-R-1019 C/G polymorphisms: effects on the negative symptom response to clozapine, Pharmacogenomics, 2015, vol. 16, no. 1, p. 35.CrossRefPubMedGoogle Scholar
  18. 18.
    Chen, C.Y., Yeh, Y.W., Kuo, S.C., et al., Catechol-O-methyltransferase gene variants may associate with negative symptom response and plasma concentrations of prolactin in schizophrenia after amisulpride treatment, Psychoneuroendocrinology, 2016, vol. 65, p. 67.CrossRefPubMedGoogle Scholar
  19. 19.
    Bosia, M., Bechi, M., Pirovano, A., et al., COMT and 5–HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia, Health Psychol. Behav. Med., 2014, vol. 2, no. 1, p. 509.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Vercammen, A., Weickert, C.S., Skilleter, A.J., et al., Common polymorphisms in dopamine-related genes combine to produce a ‘schizophrenia-like’ prefrontal hypoactivity, Transl. Psychiatry, 2014, vol. 4, no. 2, p. e356.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Tang, H., Dalton, C.F., Srisawat, U., et al., Methylation at a transcription factor-binding site on the 5–HT1A receptor gene correlates with negative symptom treatment response in first episode schizophrenia, Int. J. Neuropsychopharmacol., 2014, vol. 17, no. 4, p. 645.CrossRefPubMedGoogle Scholar
  22. 22.
    Nikiforuk, A., Hołuj, M., Kos, T., and Popik, P., The effects of a 5–HT 5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia, Neuropharmacology, 2016, vol. 105, p. 351.CrossRefPubMedGoogle Scholar
  23. 23.
    Nisenbaum, L.K., Downing, A.M., Zhao, F., et al., Serotonin 2A receptor SNP rs7330461 association with treatment response to pomaglumetadmethionil in patients with schizophrenia, J. Pers. Med., 2016, vol. 6, no. 1, p. 9.CrossRefPubMedCentralGoogle Scholar
  24. 24.
    Blasi, G., Selvaggi, P., Fazio, L., et al., Variation in dopamine D2 and serotonin 5–HT2A receptor genes is associated with working memory processing and response to treatment with antipsychotics, Neuropsychopharmacology, 2015, vol. 40, no. 7, p. 1600.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Parsons, M.J., D’Souza, U.M., Arranz, M.J., et al., The 1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity, Biol. Psychiatry, 2004, vol. 56, no. 6, p. 406.CrossRefPubMedGoogle Scholar
  26. 26.
    Myers, R.L., Airey, D.C., Manier, D.H., et al., Polymorphisms in the regulatory region of the human serotonin 5–HT2A receptor gene (HTR2A) influence gene expression, Biol. Psychiatry, 2007, vol. 61, no. 2, p. 167.CrossRefPubMedGoogle Scholar
  27. 27.
    Cabaleiro, T., López-Rodríguez, R., Ochoa, D., et al., Polymorphisms influencing olanzapine metabolism and adverse effects in healthy subjects, Hum. Psychopharmacol., 2013, vol. 28, no. 3, p. 205.CrossRefPubMedGoogle Scholar
  28. 28.
    Wilffert, B., Zaal, R., and Brouwers, J.R., Pharmacogenetics as a tool in the therapy of schizophrenia, Pharm. World Sci., 2005, vol. 27, no. 1, p. 20.CrossRefPubMedGoogle Scholar
  29. 29.
    Kim, B., Choi, E.Y., Kim, C.Y., and Song, K., Could HTR2A T102C and DRD3 Ser9Gly predict clinical improvement in patients with acutely exacerbated schizophrenia? Results from treatment responses to risperidone in a naturalistic setting, Hum. Psychopharmacol., 2008, vol. 23, no. 1, p. 61.CrossRefPubMedGoogle Scholar
  30. 30.
    Olajossy-Hilkesberger, L., Godlewska, B., Schosser-Haupt, A., et al., Polymorphisms of the 5–HT2A receptor gene and clinical response to olanzapine in paranoid schizophrenia, Neuropsychobiology, 2011, vol. 64, no. 4, p. 202.CrossRefPubMedGoogle Scholar
  31. 31.
    Reynolds, G.P., Templeman, L.A., and Zhang, Z.J., The role of 5–HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment, Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 2005, vol. 29, no. 6, p. 1021.CrossRefGoogle Scholar
  32. 32.
    Lane, H.Y., Lee, C.C., Liu, Y.C., and Chang, W.H., Pharmacogenetic studies of response to risperidone and other newer atypical antipsychotics, Pharmacogenomics, 2005, vol. 6, no. 2, p. 139.CrossRefPubMedGoogle Scholar
  33. 33.
    Wang, L., Fang, C., Zhang, A., et al., The –1019 C/G polymorphism of the 5–HT1A receptor gene is associated with negative symptom response to risperidone treatment in schizophrenia patients, J. Psychopharmacol., 2008, vol. 22, no. 8, p. 904.CrossRefPubMedGoogle Scholar
  34. 34.
    Crisafulli, C., Chiesa, A., Han, C., et al., Case-control association study for 10 genes in patients with schizophrenia: influence of 5HTR1A variation rs10042486 on schizophrenia and response to antipsychotics, Eur. Arch. Psychiatry Clin. Neurosci., 2012, vol. 262, no. 3, p. 199.CrossRefPubMedGoogle Scholar
  35. 35.
    Rajkumar, A.P., Poonkuzhali, B., Kuruvilla, A., et al., Outcome definitions and clinical predictors influence pharmacogenetic associations between HTR3A gene polymorphisms and response to clozapine in patients with schizophrenia, Psychopharmacology, 2012, vol. 224, no. 3, p. 441.CrossRefPubMedGoogle Scholar
  36. 36.
    Tang, H., Dalton, C.F., Srisawat, U., et al., Methylation at a transcription factor-binding site on the 5–HT1A receptor gene correlates with negative symptom treatment response in first episode schizophrenia, Int. J. Neuropsychopharmacol., 2014, vol. 17, no. 4, p. 645.CrossRefPubMedGoogle Scholar
  37. 37.
    Antilla, S., Kampman, O., Olli, A., et al., Association between 5–HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach, BMC Psychiatry, 2007, vol. 23, no. 7, p. 22.CrossRefGoogle Scholar
  38. 38.
    Bishop, J.R., Miller del, D., Ellingrod, V.L., and Holman, T., Association between type-three metabotropic glutamate receptor gene (GRM3) variants and symptom presentation in treatment refractory schizophrenia, Hum. Psychopharmacol., 2011, vol. 26, no. 1, p. 28.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kaur, H., Jajodia, A., Grover, S., et al., Synergistic association of PI4KA and GRM3 genetic polymorphisms with poor antipsychotic response in south Indian schizophrenia patients with low severity of illness, Am. J. Med. Genet., Part B, 2014, vol. 165, no. 8, p. 635.Google Scholar
  40. 40.
    Giegling, I., Drago, A., Dolžan, V., et al., Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol, Pharmacogenet. Genomics, 2011, vol. 21, no. 4, p. 206.PubMedGoogle Scholar
  41. 41.
    Mössner, R., Schuhmacher, A., Schulze-Rauschenbach, S., et al., Further evidence for a functional role of the glutamate receptor gene GRM3 in schizophrenia, Eur. Neuropsychopharmacol., 2008, vol. 18, no. 10, p. 768.CrossRefPubMedGoogle Scholar
  42. 42.
    Fijal, B.A., Kinon, B.J., Kapur, S., et al., Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia, Pharmacogenomics J., 2009, vol. 9, no. 5, p. 311.CrossRefPubMedGoogle Scholar
  43. 43.
    Bishop, J.R., Reilly, J.L., Harris, M.S., et al., Pharmacogenetic associations of the type-3 metabotropic glutamate receptor (GRM3) gene with working memory and clinical symptom response to antipsychotics in first-episode schizophrenia, Psychopharmacology, 2015, vol. 232, no. 1, p. 145.CrossRefPubMedGoogle Scholar
  44. 44.
    Bishop, J.R., Ellingrod, V.L., Moline, J., and Miller, D., Association between the polymorphic GRM3 gene and negative symptom improvement during olanzapine treatment, Schizophr. Res., 2005, vol. 77, nos. 2–3, p. 253.CrossRefPubMedGoogle Scholar
  45. 45.
    Harrison, P.J., Lyon, L., Sartorius, L.J., et al., The group II metabotropic glutamate receptor 3 (mGluR3, mGlu3, GRM3): expression, function and involvement in schizophrenia, J. Psychopharmacol., 2008, vol. 22, no. 3, p. 308.CrossRefPubMedGoogle Scholar
  46. 46.
    Bishop, J.R., Miller del, D., Ellingrod, V.L., and Holman, T., Association between type-three metabotropic glutamate receptor gene (GRM3) variants and symptom presentation in treatment refractory schizophrenia, Hum. Psychopharmacol., 2011, vol. 26, no. 1, p. 28. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Sacchetti, E., Magri, C. Minelli, A., et al., TheGRM7 gene, early response to risperidone, and schizophrenia: a genome-wide association study and a confirmatory pharmacogenetic analysis, Pharmacogenomics J., 2017, vol. 17, no. 2, p. 1.CrossRefGoogle Scholar
  48. 48.
    Stevenson, J.M., Reilly, J.L., Harris, M.S., et al., Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes, Transl. Psychiatry, 2016, vol. 6, no. 2, p. e739.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Chiu, H.J., Wang, Y.C., Liou, Y.J., et al., Association analysis of the genetic variants of the N-methyl D-aspartate receptor subunit 2b (NR2b) and treatment-refractory schizophrenia in the Chinese, Neuropsychobiology, 2003, vol. 47, no. 4, p. 178.CrossRefPubMedGoogle Scholar
  50. 50.
    Jajodia, A., Kaur, H., Kumari, K., et al., Evaluation of genetic association of neurodevelopment and neuroimmunological genes with antipsychotic treatment response in schizophrenia in Indian populations, Mol. Genet. Genomic Med., 2016, vol. 4, no. 1, p. 18.CrossRefPubMedGoogle Scholar
  51. 51.
    Fijal, B.A., Stouffer, V.L., Kinon, B.J., et al., Analysis of gene variants previously associated with iloperidone response in patients with schizophrenia who are treated with risperidone, J. Clin. Pychiatry, 2012, vol. 73, no. 3, p. 367.CrossRefGoogle Scholar
  52. 52.
    Drago, A., Giegling, I., Schafer, M., et al., AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment, Eur. Neuropsychopharmacol., 2013, vol. 23, no. 8, p. 887.CrossRefPubMedGoogle Scholar
  53. 53.
    Evins, A.E., Amico, E.T., Shih, V., and Goff, D.C., Clozapine treatment increases serum glutamate and aspartate compared to conventional neuroleptics, J. Neural Transm., 1997, vol. 104, nos. 6–7, p. 761.CrossRefPubMedGoogle Scholar
  54. 54.
    Sampaio, A.S., Fagerness, J., Crane, J., et al., Association between polymorphisms in GRIK2 gene and obsessive-compulsive disorder: a family-based study, CNS Neurosci. Ther., 2011, vol. 17, no. 3, p. 141.CrossRefPubMedGoogle Scholar
  55. 55.
    Greenbaum, L., Strous, R.D., Kanyas, K., et al., Association of the RGS2 gene with extrapyramidal symptoms induced by treatment with antipsychotic medication, Pharmacogenet. Genomics, 2007, vol. 17, no. 7, p. 519.CrossRefPubMedGoogle Scholar
  56. 56.
    Campbell, D.B., Lange, L.A., Skelly, T., et al., Association of RGS2 and RGS5 variants with schizophrenia symptom severity, Schizophr. Res., 2008, no. 101, p. 67.Google Scholar
  57. 57.
    Klenke, S. and Siffert, W., SNPs in genes encoding G proteins in pharmacogenetics, Pharmacogenomics, 2011, vol. 12, no. 5, p. 633.CrossRefPubMedGoogle Scholar
  58. 58.
    Suarez, B.K., Duan, J., Sanders, A.R., et al., Genomewide linkage scan of 409 European-ancestry and African American families with schizophrenia: suggestive evidence of linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the combined sample, Am. J. Hum. Genet., 2006, vol. 78, no. 2, p. 315.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Havik, B., Le Hellard, S., Rietschel, M., et al., The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia, Biol. Psychiatry, 2011, vol. 70, no. 1, p. 35.CrossRefPubMedGoogle Scholar
  60. 60.
    Ripke, S., Sanders, A.R., Kendler, K.S., et al., Genome-wide association study identifies five new schizophrenia loci, Nat. Genet., 2011, vol. 43, no. 10, p. 969.CrossRefGoogle Scholar
  61. 61.
    McClay, J.L., Adkins, D.E., Aberg, K., et al., Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics, Mol. Psychiatry, 2011, vol. 16, no. 1, p. 76.CrossRefPubMedGoogle Scholar
  62. 62.
    Noto, C., Ota, V.K., Gouvea, E.S., et al., Effects of risperidone on cytokine profile in drug-naive first-episode psychosis, Int. J. Neuropsychopharmacol., 2015, vol. 18, no. 4, p. pyu042.CrossRefPubMedCentralGoogle Scholar
  63. 63.
    Zhang, X.Y., Zhou, D.F., Cao, L.V., et al., Changes in serum interleukin-2, -6 and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia, J. Clin. Psychiatry, 2004, vol. 65, no. 7, p. 940.CrossRefPubMedGoogle Scholar
  64. 64.
    Mata, I., Crespo-Facorro, B., Rerez-Iglesias, R., et al., Association between the interleukin-1 receptor antagonist gene and negative symptom improvement during antipsychotic treatment, Am. J. Med. Genet., Part B, 2006, vol. 141, p. 939.Google Scholar
  65. 65.
    Kalmady, S.V., Venkatasubramanian, G., Shivakumar, V., et al., Relationship between Interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naive schizophrenia: evidence for differential susceptibility? PloS One, 2014, vol. 9, no. 5, p. e96021.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Ji, X., Takahashi, N., Saito, S., et al., Relationship between three serotonin receptor subtypes (HTR3A, HTR2A and HTR4) and treatment-resistant schizophrenia in Japanese population, Neurosci. Lett., 2008, vol. 435, no. 2, p. 95.CrossRefPubMedGoogle Scholar
  67. 67.
    Zhang, J.P., Lencz, T., Geisler, S., et al., Genetic variation in BDNF is associated with antipsychotic treatment resistance in patients with schizophrenia, Schizophr. Res., 2013, vol. 146, p. 285.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Jenkins, A., Apud, J.A., Zhang, F., et al., Identification of candidate single-nucleotide polymorphisms in NRXN1 related to antipsychotic treatment response in patients with schizophrenia, Neuropsychopharmacology, 2014, vol. 39, no. 9, p. 2170.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Jajodia, A., Kaur, H., Kumari, K., et al., Evaluation of genetic association of neurodevelopment and neuroimmunological genes with antipsychotic treatment response in schizophrenia in Indian populations, Mol. Genet. Genomic Med., 2016, vol. 4, no. 1, p. 18.CrossRefPubMedGoogle Scholar
  70. 70.
    Kang, S.G., Chee, I.S., Lee, K., and Lee, J., rs7968606 polymorphism of ANKS1B is associated with improvement in the PANSS general score of schizophrenia caused by amisulpride, Hum. Psychopharmacol., 2017, vol. 32, no. 2. doi 10.1002/hup.2562Google Scholar
  71. 71.
    Spellmann, I., Riedel, M., Städtler, J., et al., Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment, Cognit. Neuropsychiatry, 2017, vol. 22, no. 4, p. 280.CrossRefGoogle Scholar
  72. 72.
    Zheng, M., Zhang, H., Dill, D.L., et al., The role of ABCB5 alleles in susceptibility to haloperidol-induced toxicity in mice and humans, PLoS Med., 2015, vol. 12, no. 2, p. e1001782.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Nnadi, C.U. and Malhotra, A.K., Individualizing antipsychotic drug therapy in schizophrenia: the promise of pharmacogenetics, Curr. Psychiatry Rep., 2007, vol. 9, no. 4, p. 313.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Lee, S.T., Ryu, S., Kim, S.R., et al., Association study of 27 annotated genes for clozapine pharmacogenetics: validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response, J. Clin. Psychopharmacol., 2012, vol. 32, no. 4, p. 441.CrossRefPubMedGoogle Scholar
  75. 75.
    Koga, A.T., Strauss, J., Zai, C., et al., Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study, J. Neural Transm., 2016, vol. 123, no. 3, p. 329.CrossRefPubMedGoogle Scholar
  76. 76.
    Ramsey, T.L., Liu, Q., and Brennan, M.D., Replication of SULT4A1-1 as a pharmacogenetic marker of olanzapine response and evidence of lower weight gain in the high response group, Pharmacogenomics, 2014, vol. 15, no. 7, p. 933.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Mannheimer, B., Haslemo, T., Lindh, J.D., et al., Risperidone and venlafaxine metabolic ratios strongly predict a CYP2D6 poor metabolizing genotype, Ther. Drug Monit., 2016, vol. 38, no. 1, p. 127.CrossRefPubMedGoogle Scholar
  78. 78.
    Saito, M., Yasui-Furukori, N., and Kaneko, S., Clinical pharmacogenetics in the treatment of schizophrenia, Nihon Shinkei Seishin Yakurigaku Zasshi, 2005, vol. 25, no. 3, p. 129.PubMedGoogle Scholar
  79. 79.
    Suzuki, T., Mihara, K., Nakamura, A., et al., Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia, Ther. Drug Monit., 2011, vol. 33, no. 1, p. 21.CrossRefPubMedGoogle Scholar
  80. 80.
    Brandl, E.J., Chowdhury, N., Tiwari, A.K., et al., Genetic variation in CYP3A43 is associated with response to antipsychotic medication, J. Neural Transm., 2015, vol. 122, no. 1, p. 29.CrossRefPubMedGoogle Scholar
  81. 81.
    Cabaleiro, T., Ochoa, D., Román, M., et al., Polymorphisms in CYP2D6 have a greater effect on variability of risperidone pharmacokinetics than gender, Basic Clin. Pharmacol. Toxicol., 2015, vol. 116, no. 2, p. 124.CrossRefPubMedGoogle Scholar
  82. 82.
    Suzuki, T., Mihara, K., Nakamura, A., et al., Effects of genetic polymorphisms of CYP2D6, CYP3A5, and ABCB1 on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia, Ther. Drug Monit., 2014, vol. 36, no. 5, p. 651.CrossRefPubMedGoogle Scholar
  83. 83.
    Viikki, M., Kampman, O., Seppälä, N., et al., CYP1A2 polymorphism –1545C > T (rs2470890) is associated with increased side effects to clozapine, BMC Psychiatry, 2014, vol. 14, no. 1, p. 50.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Fernø, J., Ersland, K.M., Duus, I.H., and González-García, I., Olanzapine depot exposure in male rats: dose-dependent lipogenic effects without concomitant weight gain, Eur. Neuropsychopharmacol., 2015, vol. 25, no. 6, p. 923.CrossRefPubMedGoogle Scholar
  85. 85.
    Sluis, R.J., Nahon, J.E., Reuwer, A.Q., et al., Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice, Br. J. Pharmacol., 2015, vol. 172, no. 9, p. 2397.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Zhang, C., Zhang, Y., Cai, J., et al., Complement 3 and metabolic syndrome induced by clozapine: a cross-sectional study and retrospective cohort analysis, Pharmacogenomics J., 2017, vol. 17, no. 1, p. 92.CrossRefPubMedGoogle Scholar
  87. 87.
    Snopov, S.A., Teryukova, N.P., Sakhenberg, E.I., Teplyashina, V.V., and Nasyrova, R.F., Use of HepG2 cell line for evaluation of toxic and metabolic antipsychotic action, Cell Tissue Biol., 2017, vol. 11, no. 5, p. 405.CrossRefGoogle Scholar
  88. 88.
    Fonseka, T.M., Tiwari, A.K., Gonçalves, V.F., et al., The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain, World J. Biol. Psychiatry, 2015, vol. 16, no. 1, p. 45.CrossRefPubMedGoogle Scholar
  89. 89.
    Nussbaum, L.A., Dumitraşcu, V., Tudor, A., et al., Molecular study of weight gain related to atypical antipsychotics: clinical implications of the CYP2D6 genotype, Rom. J. Morphol. Embryol., 2014, vol. 55, no. 3, p. 877.PubMedGoogle Scholar
  90. 90.
    Ono, S., Suzuki, Y., Fukui, N., et al., GIPR gene polymorphism and weight gain in patients with schizophrenia treated with olanzapine, J. Neuropsychiatry Clin. Neurosci., 2015, vol. 27, no. 2, p. 162.CrossRefPubMedGoogle Scholar
  91. 91.
    Popp, J., Leucht, S., Heres, S., and Steimer, W., DRD4 48 bp VNTR but not 5–HT2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain, Pharmacogenomics J., 2009, vol. 9, no. 1, p. 71.CrossRefPubMedGoogle Scholar
  92. 92.
    Gunes, A., Melkersson, K.I., Scordo, M.G., and Dahl, M.L., Association between HTR2C and HTR2A polymorphisms and metabolic abnormalities in patients treated with olanzapine or clozapine, J. Clin. Psychopharmacol., 2009, vol. 29, no. 1, p. 65.CrossRefPubMedGoogle Scholar
  93. 93.
    Kang, S.H., Lee, J.I., Han, H.R., et al., Polymorphisms of the leptin and HTR2C genes and clozapine-induced weight change and baseline BMI in patients with chronic schizophrenia, Psychiatr. Genet. (London), 2014, vol. 24, no. 6, p. 249.CrossRefGoogle Scholar
  94. 94.
    Klemettilä, J.P., Kampman, O., Seppälä, N., et al., Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia, Eur. Psychiatry, 2015, vol. 30, no. 2, p. 296.CrossRefPubMedGoogle Scholar
  95. 95.
    Ellingrod, V.L., Bishop, J.R., Moline, J., et al., Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia, Psychopharmacol. Bull., 2007, vol. 40, no. 1, p. 57.PubMedGoogle Scholar
  96. 96.
    Perez-Iglesias, R., Mata, I., Amado, J.A., et al., Effect of FTO, SH2B1, LEP, and LEPR polymorphisms on weight gain associated with antipsychotic treatment, J. Clin. Psychopharmacol., 2010, vol. 30, no. 6, p. 661.CrossRefPubMedGoogle Scholar
  97. 97.
    Song, X., Pang, L., Feng, Y., et al., Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia, Behav. Brain Funct., 2014, vol. 10, no. 1, p. 1.CrossRefGoogle Scholar
  98. 98.
    Le Hellard, S., Theisen, F.M., Haberhausen, M., et al., Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? Mol. Psychiatry, 2008, vol. 15, no. 1, p. 854.Google Scholar
  99. 99.
    Yang, L., Chen, J., Liu, D., et al., Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia, Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 2015, vol. 56, p. 136.CrossRefGoogle Scholar
  100. 100.
    Roffeei, S.N., Mohamed, Z., Reynolds, G.P., et al., Association of FTO, LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics, Pharmacogenomics, 2014, vol. 15, no. 4, p. 477.CrossRefPubMedGoogle Scholar
  101. 101.
    Hong, C.J., Liou, Y.M., Bai, T.T., et al., Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment, Pharmacogenet. Genomics, 2010, vol. 20, no. 6, p. 359.CrossRefPubMedGoogle Scholar
  102. 102.
    Tiwari, A.K., Zai, C.C., Likhodi, O., et al., Association study of cannabinoid receptor 1 (CNR1) gene in tardive dyskinesia, Pharmacogenomics, 2011, vol. 12, no. 3, p. 260.CrossRefGoogle Scholar
  103. 103.
    Hu, X., Zhou, H., Zhang, D., et al., Clozapine protects dopaminergic neurons from inflammation-induced damage by inhibiting microglial overactivation, J. Neuroimmune Pharmacol., 2012, vol. 7, no. 1, p. 187.CrossRefPubMedGoogle Scholar
  104. 104.
    Lencz, T., Robinson, D.G., Napolitano, B., et al., DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia, Pharmacogenet. Genomics, 2010, vol. 20, no. 9, p. 569.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Goldstein, J.I., Jarskog, L.F., Hilliard, C., et al., Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles, Nat. Commun., 2014, vol. 5, p. 4757.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Liou, Y.J., Wang, Y.C., Chen, J.Y., et al., Association analysis of polymorphisms in the N-methyl-D-aspartate (NMDA) receptor subunit 2B (GRIN2B) gene and tardive dyskinesia in schizophrenia, Psychiatry Res., 2007, vol. 153, no. 3, p. 271.CrossRefPubMedGoogle Scholar
  107. 107.
    Zai, C.C., Wang, Y.C., Chen, J.Y., et al., Association study of tardive dyskinesia and twelve DRD2 polymorphisms in schizophrenia patients, Int. J. Neuropsychopharmacol., 2007, vol. 10, no. 5, p. 639.CrossRefPubMedGoogle Scholar
  108. 108.
    Zhang, Z., Hou, G., Zhang, X.B., and Yao, H., Pharmacogenetic assessment of antipsychotic-induced tardive dyskinesia: contribution of 5-hydroxytryptamine 2C receptor gene and of combination of dopamine D3 variant allele (Gly) and MNSOD wild allele (Val), Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2003, vol. 20, no. 2, p. 98.PubMedGoogle Scholar
  109. 109.
    Bakker, P.R., van Harten, P.N., and van Os, J., Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions, Mol. Psychiatry, 2008, vol. 13, no. 5, p. 544.CrossRefPubMedGoogle Scholar
  110. 110.
    Zai, C.C., Tiwari, A.K., Basile, V., et al., Association study of tardive dyskinesia and five DRD4 polymorphisms in schizophrenia patients, Pharmacogenomics J., 2009, vol. 9, no. 3, p. 168.CrossRefPubMedGoogle Scholar
  111. 111.
    Tiwari, A.K., Zai, C.C., Likhodi, O., et al., Association study of cannabinoid receptor 1 (CNR1) gene in tardive dyskinesia, Pharmacogenomics J., 2011, vol. 12, no. 3, p. 260.CrossRefPubMedGoogle Scholar
  112. 112.
    Rajagopal, V., Sundaresan, L., Rajkumar, A.P., et al., Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea, Psychiatr. Genet. (London), 2014, vol. 24, no. 6, p. 273.CrossRefGoogle Scholar
  113. 113.
    Knol, W., van Marum, R.J., Jansen, P.A., et al., Genetic variation and the risk of haloperidol-related parkinsonism in elderly patients: a candidate gene approach, J. Clin. Psychopharmacol., 2013, vol. 33, no. 3, p. 405.CrossRefPubMedGoogle Scholar
  114. 114.
    Solismaa, A., Kampman, O., Seppälä, N., et al., Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment, Hum. Psychopharmacol., 2014, vol. 29, no. 4, p. 336.CrossRefPubMedGoogle Scholar
  115. 115.
    Greenbaum, L., Smith, R.C., Rigbi, A., et al., Further evidence for association of the RGS2 gene with antipsychotic-induced parkinsonism: protective role of a functional polymorphism in the 3′-untranslated region, Pharmacogenomics J., 2009, vol. 9, no. 2, p. 103.CrossRefPubMedGoogle Scholar
  116. 116.
    Fedorenko, O.Y., Loonen, A.J., Lang, F., et al., Association study indicates a protective role of phosphatidylinositol-4-phosphate-5-kinase against tardive dyskinesia, Int. J. Neuropsychopharmacol., 2015, vol. 18, no. 6, p. 1.CrossRefGoogle Scholar
  117. 117.
    Saito, T., Ikeda, M., Mushiroda, T., et al., Pharmacogenomicstudy of clozapine-induced agranulocytosis/granulocytopenia in a Japanese population, Biol. Psychiatry, 2016, vol. 80, no. 8, p. 636.CrossRefPubMedGoogle Scholar
  118. 118.
    Kelly, D.L., Kreyenbuhl, J., Dixon, L., et al., Clozapine underutilization and discontinuation in African Americans due to leucopenia, Schizophr. Bull., 2007, vol. 33, no. 5, p. 1221.CrossRefPubMedGoogle Scholar
  119. 119.
    De Leon, J., Correa, J.C., Ruaño, G., et al., Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels, Schizophr. Res., 2008, vol. 98, no. 1, p. 40.CrossRefPubMedGoogle Scholar
  120. 120.
    Brener, S. and Holubowich, C., Pharmacogenomic testing for psychotropic medication selection: a systematic review of the Assurex GeneSight Psychotropic test, Ont. Health Technol. Assess. Ser., 2017, vol. 17, no. 4, p. 1.Google Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  1. 1.Institute of Biochemistry and Genetics, Ufa Federal Research Centre , Russian Academy of SciencesUfaRussia
  2. 2.Bashkir State Medical UniversityUfaRussia

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