The article presents the results of the study of the relationship between the risk of acute drug-induced extrapyramidal disorders in antipsychotic therapy of schizophrenia with the gene polymorphism of neurometabolism and the xenobiotic detoxification system: CYP2D6, DRD2, GST-M1, GST-T1, MDR1 and COMT. Found that the risk of acute drug-induced Parkinsonism linked to the carriage of allele «slow» metabolism of CYP2D6 * 4 (rs3892097) in the gene CYP2D6 and allele A2 increased gene expression level DRD2 polymorphic locus DRD2 / ANKK1 Taq1A (rs1800497) in ANKK1 gene, as well as the carriage T / T genotype of the MDR1 polymorphic locus (C3435T). Acute drug-induced akatisia found a connection with deletions in the genes GST-M1, GST-T1, which are responsible for the functioning of the glutathione xenobiotic detoxification system. The results of the polymorphism of these genes allows us to individualize the antipsychotic therapy of patients with paranoid schizophrenia, taking into account the risk of acute extrapyramidal disorders in them.

1. Jablensky A. (2000) Epidemiology of schizophrenia: theglobal bur denof diseaseand disability. EurArchPsychiatry ClinNeurosci. Vol. 250, no. 6, pp. 274–285.

2. Gerlach J, Peacock L. (1995) New antipsychotics: the present status. In ClinPsychopharmacol. Vol. 10, pp. 39–48.

3. Steck H. (2006) Extrapyramidal and diencephalic syndrome in the course of largactil and serpasil treatments. Ann Med Psychol (Paris). Vol. 12, pp. 737–744.

4. Poyurovsky M. (2010). Acute antipsychotic-induced akathisia revisited. BrJPsychiatry. Vol. 196, no.2, pp. 89–91.

5. Plotnikova E. V. (2009) Lekarstvenno-inducirovanny edvigatelnyerasstrojstvaprishizofrenii. Tavricheskijmedikobiologicheskijvestnik. T. 12, № 1 (45). S. 192–199.

6. Sachdev P. (2004) Earl y extrapyramidal side-effects as risk factors for later tardive dyskinesia: a prospective study. Aust N Z J Psychiatry. Vol. 38, no. 6, pp. 445–9.

7. Duncan E. J., Adler L. A., Stephanides M. et al. (2000) Akathisia and exacerbation of psychopathology: a preliminary report. ClinNeuropharmacol. Vol. 23, pp. 169–173.

8. Peitl M. V., Prološčić J., Blažević-Zelić S. (2011) Et al. Symptoms of agitated depression and/or akathisia.PsychiatrDanub. Vol. 23, no 1, pp. 108–110.

9. Reid A. M., McNamara J. P, Murphy T. K. (2015) Sideeffects of SSRIs disrupt multimodal treatment for pediatric OCD in a randomized-controlled trial. J Psychiatr Res. Vol. 71, pp. 140–147.

10. Lipinski J. F. Jr., Mallya G., Zimmerman P. et al. (1989) Fluoxetine-induced akathisia: clinical and theoretical implications. J Clin Psychiatry. Vol. 50, no. 9, pp. 339–342.

11. Temmingh H., Stein D. J. (2015) Anxiety in Patients with Schizophrenia: Epidemiology and Management. CNS Drugs. Vol. 29, no. 10, pp. 819–832.

12. Fedorova N. V., Vetohina T. N. (2009) Diagnostika ilechenien ejrolepticheskihj ekstrapiramidnyh sindromov. Psih. rasstrojstva v obshhej medicine. № 3.

13. Bekker R. A., BykovJu.V. Akatizija: klinicheskija naliz patologii s rekomendacija miiobzoromliteratury. ConsiliumMedicum: Publikaciipartnerov.

14. Lohr J. B., Eidt C. A., AbdulrazzaqAlfaraj A. et al. (2015) The clinical challenges of akathisia. CNS Spectr. Vol. 20, pp. 15–16 Availabe:https://www.ncbi.nlm.nih.gov/pubmed/26683525.

15. Miller C. H., Hummer M., Oberbauer H. et al. Risk factors for the development of neuroleptic induced akathisia. EurNeuropsychopharmacol. 1997;7(1):51–55.

16. Nordstrцm P., Michaлlsson K., Gustafson Y. et al. Traumatic braininjury and young onset dementia: a nationwide cohort study. Ann Neurol. 2014;75(3):374–381.

17. Wright M. T. Antiemetics, akathisia, and pregnancy. Psychosomatics. 2007;48(6):461–466.

18. Genomewide association study of movement-related adverse antipsychotic effects.Aberg K, Adkins DE, Bukszár J, Webb BT, Caroff SN, Miller DD et al. // Biol Psychiatry. – 2010. – Vol. 67. – P. 279–282.

19. Genome-wideassociation study of antipsychoticinduced parkinsonism severity among schizophrenia patients. AlkelaiA, GreenbaumL, RigbiA. et al. // Psychopharmacol (Berl). –2009. – Vol. 206. – P. 491–499.

20. Drago A, Crisafulli C, Serretti A. The genetics of antipsychotic induced tremors: agenome-wide pathway analysis on the STEP-BDSCP sample.// Am J Med Genet B Neuropsychiatr Genet. – 2011. – Vol. 156B. – P. 975–986.

21. Pharmacogenetics and antipsychotic treatment response. NaumovskaZ, NestorovskaA. K, FilipceA, Etal // Prilozi. – 2015. – Vol. 361, № 1. – P. 53–67.

22. Plesničar B. K. Personalized antipsychotic treatment: the adverseeffects perspectives // PsychiatriaDanubina. – 2010. – Vol. 22, № 2. – P. 329–334.

23. Фармакогенетический подход к оценке риска развития индуцированных антипсихотиками экстрапирамидных нарушений К. А. Кирничная Д. Н. Сосин М. В. Иванов и др. // Журнал неврологии и психиатрии им. С. С. Корсакова. – 2015. – Vol. 4. – P. 113–125.

24. MacNeil RR, Müller DJ. Genetics of Common Antipsychotic-Induced Adverse Effects. // Mol Neuropsychiatry. – 2016. – Vol. 2, No 2. – P. 61–78.

25. De Leon J. Pharmacogenomics: the promise of personalized medicine for CNS disorders. Neuropsychopharmacology. – 2009. – Vol. 34 (1). – Р. 159–72.

26. Plesnicar BK, Zalar B, Breskvar K, Dolzan V. The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on longterm antipsychotic treatment. J. Psychopharmacol. 2006;20(6):829–833.

27. Kastelic M, Koprivsek J, Plesnicar BK, Serretti A, Mandelli L, Locatelli I, Grabnar I, Dolzan V. MDR1 gene polymorphisms and response to acute risperidone treatment. ProgNeuropsychopharmacolBiol Psychiatry. 2010;34(2): 387–392.

28. Zivković M, Mihaljević-Peles A, Bozina N, Sagud M, Nikolac-Perkovic M, Vuksan-Cusa B, Muck-Seler D. The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol. JClinPsychopharmacol. 2013;33(5):593–599.

29. О. В. Горгун, И. М. Голоенко, В. Г. Объедков Лекарственно индуцированнаяакатизия у пациентов с шизофренией: литературный обзор. // Психиатрия, психотерапия и клиническая психология № 3 (8) 2017 г. – С. 422–431.

30. Chouinard G, Ross-Chouinard A, Annable L, et al.: Extrapyramidal Rating Scale. The Canadian Journal of Neurological Sciences 7:233–239, 1980.

31. Patsopoulos NA, Ntzani EE, Zintzaras E, Ioannidis JP. CYP2D6 polymorphisms and the risk of tardive dyskinesia in schizophrenia: a meta-analysis. PharmacogenetGenomi cs.2005;15(3):151–158.

32. Bakker PR, van Harten PN, van Os J. Antipsychoticinduced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a metaanalysis of pharmacogenetic interactions. Mol Psychiatry. 2008;13(5):544–556.

33. De Leon J, Susce MT, Pan RM, Koch WH, WedlundPJ. Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. JClinPsychopharmacol. 2005;25(5):448–456.

34. De Luca V, Souza RP, Viggiano E, Zai CC, Shinkai T, Lieberman JA, Potkin SG, Meltzer HY, Remington G, Kennedy JL. MDR1 gene in tardive dyskinesia scale scores: comparison of strategies for quantitative trait haplotype analysis. SchizophrRes. 2009;110(1–3):200–201.

35. Докукина Т. В. Метод определения полиморфизма гена MDR1 у пациентов, страдающих расстройствами шизофренического спектра, для индивидуализации лечения антипсихотическими лекарственными средствами: инструкция по применению./ Т. В. Докукина, А. А. Гелец, Т. С. Голубева, М. В. Махров и др. РНПЦ психического здоровья, ГНУ «Институт биоорганической химии». Минск, 2015. – 9 с.

36. Zai CC, DeLuca V, Hwang RW, Voineskos A, Müller DJ, Remington G, Kennedy JL. Meta-analysis of two dopamine D2 receptor gene polymorphisms with tardive dyskinesia in schizophrenia patients.MolPsychiat ry.2007;12(9):794–795.

37. Белоусов Ю. Б., Кукес В. Г., Лепахин В. К., Петров В. И. (2009) Клиническая фармакология: национальное руководство. – М.: ГОЭТАР-Медиа. – С. 854–868.

38. Kang SG, Lee HJ, Choi JE, An H, Rhee M, Kim L. Association study between glutathione S-transferase GST-M1, GST-T1, and GST-P1 polymorphisms and tardive dyskinesia. Hum Psychopharmacol.2009;24:55–6