Входя на эту страницу, Вы подтверждаете, что являетесь  медицинским работником.

Status message

Not the entire site translated, but only to "Magazine"

Genetic markers of metabolic side-effects risks in second-generation antipsychotic therapy

G.E. Mazo1, A.O. Kibitov2
1Bekhterev’s National medical research center of psychiatry and neurology, Ministry of health of Russian Federation, Saint-Petersburg
2Serbsky’s National medical research center of psychiatry and neurology, Ministry of health of Russian Federation, Moscow

The serious side-effects of second-generation antipsychotic (SGA) therapy are the metabolic disorders such as increase in body mass, obesity, disorders of carbohydrate and lipid metabolism (dyslipidemia, hyperglycemia, insulin resistance) and metabolic syndrome. The aim of our review was to analyze the current data about the risks markers of metabolic side-effects during SGA treatment. It was shown that the major role belongs to the genes responsible for the central control of eating behavior (hypothalamus, “reward”-system) and to the genes of (in-) direct “targets” of SGA. The genes of metabolic, endocrine and peripheral eating behavior systems play the modulate role. It is possible that the influence of the genetic systems of peripheral metabolic disorders (lipid and carbohydrate systems) is especially important in patients with high genetic risks of these disorders. In those cases SGA are the pharmacological “triggers” of risks leading to the rapid and severe clinical manifestation of metabolic disorders. It is obvious that the special genetic panels are necessary for the preventive diagnostics of individual metabolic side-effects risks of SGA treatment. The panels should include the genes of eating behavior, lipid and carbohydrate metabolism. These diagnostic procedures will clinically result in the possibility of the individual treatment with the safest SGA agent.

References: 

1. Gurovich I.Ya., Uzbekov M.G. K ponimaniyu biomarkerov psikhicheskikh rasstroistv // Sotsial'naya i klinicheskaya psikhiatriya. – 2015. – № 3. – S. 80–83.

2. Bagdy G., Juhasz G. Biomarkers for personalised treatment in psychiatric diseases // Expert Opin Med Diagn. – 2013. – Vol. 7, No. 5. – P. 417–422.

3. Schmitt A., Martins-de-Souza D., Akbarian S., Cassoli J.S., Ehrenreich H., Fischer A., Fonteh A., Gattaz W.F., Gawlik M., Gerlach M., Grünblatt E., Halene T., Hasan A., Hashimoto K., Kim Y.K., Kirchner S.K., Kornhuber J., Kraus T.F., Malchow B., Nascimento J.M., Rossner M., Schwarz M., Steiner J., Talib L., Thibaut F., Riederer P., Falkai P. Members of the WFSBP Task Force on Biological Markers. Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for Biomarkers and Endophenotypes of Schizophrenia, Part III: Molecular Mechanisms // World J Biol Psychiatry. – 2017. – Aug. – Vol. 18, No. 5. – R. 330–356.

4. Mazo G.E., Kibitov A.O. Kompleksnaya model' upravleniya riskami razvitiya metabolicheskikh narushenii pri ispol'zovanii atipichnykh antipsikhotikov // Psikhicheskoe zdorov'e. – 2016. – T. 14, № 11 (126). – S. 34–45.

5. Kibitov A.O., Ivashchenko D.V., Sychev D.A. Farmakogeneticheskii podkhod k povysheniyu effektivnosti i bezopasnosti antipsikhoticheskoi farmakoterapii shizofrenii // Sovremennaya terapiya psikhicheskikh rasstroistv. – 2017. – № 1. – S. 2–13. DOI: 10.21265/PSYPH.2017.40.4982.

6. Alfimov P.V., Ryvkin P.V., Ladyzhenskii M.Ya., Mosolov S.N. Metabolicheskii sindrom u bol'nykh shizofreniei (obzor literatury) // Sovremennaya terapiya psikhicheskikh rasstroistv. – 2014. – № 3. – S. 8–14.

7. Gorobets L.N., Mazo G.E. Neiroendokrinnye disfunktsii pri ispol'zovanii psikhofarmakoterapii: klinika, diagnostika, faktory riska i korrektsiya. // Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. – 2014. – № 10. – C. 85–93.

8. Gorobets L.N., Bulanov V.S., Vasilenko L.M., Litvinov A.V., Polyakovskaya T.P. Metabolicheskie rasstroistva u bol'nykh shizofreniei v protsesse terapii atipichnymi antipsikhoticheskimi preparatami // Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. – 2012. – T. 112, № 9. – S. 90–96.

9. Rojo L.E., Gaspar P.A., Silva H., Risco L., Arena P., Cubillos-Robles K., Jara B. Metabolic syndrome and obesity among users of second generation antipsychotics: A global challenge for modern psychopharmacology // Pharmacol Res. – 2015. – Nov. – Vol. 10, No. 1. – R. 74–85.

10. Cuerda C., Velasco C., Merchán-Naranjo J., García-Peris P., Arango C. The effects of second-generation antipsychotics on food intake, resting energy expenditure and physical activity // Eur J Clin Nutr. – 2014. – Feb. – Vol. 68, No. 2. – R. 146–152.

11. Mosolov S.N., Kabanov S.O. Metabolicheskie narusheniya pri antipsikhoticheskoi terapii // Sotsial'naya i klinicheskaya psikhiatriya. – 2003. – T. 13, № 2. – S. 162–172.

12. Hasan A., Falkai P., Möller H.J., Wobrock T., Lieberman J., Glenthoj B., Gattaz W.F., Thibaut F., Mosolov S. World federation of societies of biological psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects // The World Journal of Biological Psychiatry: the official journal of the World Federation of Societies of Biological Psychiatry. – 2013. – Vol. 14, No. 1. – P. 2–44.

13. Mosolov S.N., Ryvkin P.V., Serditov O.V., Ladyzhenskii M.Ya., Potapov A.V. Metabolicheskie pobochnye effekty sovremennoi antipsikhoticheskoi farmakoterapii // Sotsial'naya i klinicheskaya psikhiatriya. – 2008. – T. 18, № 3. – S. 75–90.

14. Henderson D.C., Vincenzi B., Andrea N.V., Ulloa M., Copeland P.M. Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses // Lancet Psychiatry. – 2015. – May. − Vol. 2, No. 5. – R. 452–464.

15. Otanfio L.M., Izquierdoa L.B., Mondragón A.G., Pinedo M.A., Ayerdi I.Q. After six months of anti-psychotic treatment: Is the improvement in mental health at the expense of physical health? // Rev Psiquiatr Salud Ment (Barc.). – 2013. – Vol. 6, No. 1. – R. 26−32.

16. Bak M., Fransen A., Janssen J., van Os J., Drukker M. Almost All Antipsychotics Result in Weight Gain: A Meta-Analys // PLoS ONE. – 2014. – Vol. 9, No. 4. – R. 94–112.

17. Green M., Marder S., Glynn S. The neurocognitive effects of low-dose haloperidol: A two-year comparison with risperidone // Biol Psychiatry – 2002. – Vol. 51, No. 12. – P. 972–978.

18. Newcomer J.W., Haupt D.W. The metabolic effects of antipsychotic medications // Can J Psychiatry. – 2006. – Jul. – Vol. 51, No. 8. – R. 480–491.

19. Dent R., Blackmore A., Peterson J., Habib R., Kay G.P., Gervais A., Taylor V., Wells G. Changes in body weight and psychotropic drugs: a systematic synthesis of the literature // PLoS One. – 2012. – Vol. 7, No. 6. – R. 368–389.

20. Musil R., Obermeier M., Russ P., Hamerle M. Weight gain and antipsychotics: a drug safety review // Expert Opin Drug Saf. – 2015. – Jan. − Vol. 14, No. 1. – R. 73−96.

21. Rummel-Kluge C., Komossa K., Schwarz S., Hunger H., Schmid F., Lobos C.A., Kissling W., Davis J.M., Leucht S. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis // Schizophr Res. – 2010. – Nov. – Vol. 123, No. 2–3. – R. 225–233.

22. Malhotra N., Grover S., Chakrabarti S., Kulhara P. Metabolic syndrome in schizophrenia // Indian J Psychol Med. – 2013. – Vol. 35, No. 3. – R. 227–240.

23. Leucht S., Heres S., Kissling W., Davis J.M. Evidence-based pharmacotherapy of schizophrenia // Int J Neuropsychopharmacol. – 2014. – Vol. 14, No. 2. – R. 269–284.

24. Devlin A.M., Panagiotopoulos C. Metabolic side effects and pharmacogenetics of second-generation antipsychotics in children // Pharmacogenomics. – 2015. – Vol. 16, No. 9. – R. 981–996.

25. Roerig J.L., Steffen K.J., Mitchell J.E. Atypical antipsychotic-induced weight gain: insights into mechanisms of action // CNS Drugs. – 2011. – Dec. 1. – Vol. 25, No. 12. – R. 1035–1059.

26. Müller D.J., Kennedy J.L. Genetics of antipsychotic treatment emergent weight gain in schizophrenia // Pharmacogenomics. – 2006. – Sep. − Vol. 7, No. 6. – R. 863–887.

27. Reynolds G.P., Hill M.J., Kirk S.L. The 5-HT2C receptor and antipsychoticinduced weight gain – mechanisms and genetics // J Psychopharmacol. – 2006. – Jul. − Vol. 20, Suppl. 4. – R. 15–18.

28. Lett T.A., Wallace T.J., Chowdhury N.I., Tiwari A.K., Kennedy J.L., Müller D.J. Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications // Mol Psychiatry. – 2012. – Mar. – Vol. 17, No. 3. − R. 242–266.

29. Brandl E.J., Kennedy J.L., Müller D.J. Pharmacogenetics of antipsychotics // Can J Psychiatry. – 2014. – Vol. 59, No. 2. – R. 76–88.

30. Müller D.J., Chowdhury N.I., Zai C.C. The pharmacogenetics of antipsychotic-induced adverse events /// Curr Opin Psychiatry. – 2013. – Vol. 26, No. 2. – R. 144–150.

31. Ma X., Maimaitirexiati T., Zhang R., Gui X., Zhang W., Xu G., Hu G. HTR2C polymorphisms, olanzapine-induced weight gain and antipsychotic-induced metabolic syndrome in schizophrenia patients: A meta-analysis // Int J Psychiatry Clin Pract. – 2014. – Vol. 18, No. 4. – R. 229–242.

32. Arranz M.J., Rivera M., Munro J.C. Pharmacogenetics of response to antipsychotics in patients with schizophrenia // CNS Drugs. – 2011. – Nov. 1. − Vol. 25, No. 11. – R. 933–969.

33. Suetani R.J., Siskind D., Reichhold H., Kisely S. Genetic variants impacting metabolic outcomes among people on clozapine: a systematic review and meta-analysis // Psychopharmacology (Berl). – 2017. – Sep. 6. – Vol. 234, Issue 20. – P. 2989–3008.

34. Zhang J.P., Lencz T., Zhang R.X., Nitta M., Maayan L., John M., Robinson D.G., Fleischhacker W.W., Kahn R.S., Ophoff R.A., Kane J.M., Malhotra A.K., Correll C.U. Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis // Schizophr Bull. – 2016. – Vol. 42, Issue 6. – P. 1418–1437.

35. Brennan M.D. Pharmacogenetics of second-generation antipsychotics // Pharmacogenomics. – 2014. – Apr. − Vol. 15, No. 6. – R. 869–884.

36. Ujike H., Nomura A., Morita Y., Morio A., Okahisa Y., Kotaka T., Kodama M., Ishihara T., Kuroda S. Multiple genetic factors in olanzapine-induced weight gain in schizophrenia patients: a cohort study // J Clin Psychiatry. – 2008. – Sep. − Vol. 69, No. 9. – R. 1416–1422.

37. Hong C.J., Liou Y.J., Bai Y.M., Chen T.T., Wang Y.C., Tsai S.J. Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment // Pharmacogenet Genomics. – 2010. – Jun. − Vol. 20, No. 6. – R. 359–366.

38. Lencz T., Robinson D.G., Napolitano B., Sevy S., Kane J.M., Goldman D., Malhotra A.K. DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia // Pharmacogenet Genomics. – 2010. – Sep. − Vol. 20, No. 9. – R. 569–572.

39. Houston J.P., Kohler J., Bishop J.R., Ellingrod V.L., Ostbye K.M., Zhao F., Conley R.R., Poole Hoffmann V., Fijal B.A. Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia // J Clin Psychiatry. – 2012. – Aug. − Vol. 73, No. 8. – R. 1077–1086.

40. Tiwari A.K., Brandl E.J., Weber C., Likhodi O., Zai C.C., Hahn M.K., Lieberman J.A., Meltzer H.Y., Kennedy J.L., Müller D.J. Association of a functional polymorphism in neuropeptide Y with antipsychotic-induced weight gain in schizophrenia patients // J Clin Psychopharmacol. – 2013. – Feb. − Vol. 33, No. 1. – R. 11–17.

41. Yu W., De Hert M., Moons T., Claes S.J., Correll C.U., van Winkel R. CNR1 gene and risk of the metabolic syndrome in patients with schizophrenia // J Clin Psychopharmacol. – 2013. – Apr. − Vol. 33, No. 2. – R. 186–192.

42. Jassim G., Fernø J., Theisen F.M., Haberhausen M., Christoforou A., Håvik B., Gebhardt S., Remschmidt H., Mehler-Wex C., Hebebrand J., Lehellard S., Steen V.M. Association study of energy homeostasis genes and antipsychotic-induced weight gain in patients with schizophrenia // Pharmacopsychiatry. – 2011. – Jan. − Vol. 44, No. 1. – R. 15–20.

43. Czerwensky F., Leucht S., Steimer W. Association of the common MC4R rs17782313 polymorphism with antipsychotic-related weight gain // J Clin Psychopharmacol. – 2013. – Feb. − Vol. 33, No. 1. – R. 74–79.

44. Ellingrod V.L., Bishop J.R., Moline J., Lin Y.C., Miller D.D. 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. – R. 57–62.

45. Hong C.J., Chen T.T., Bai Y.M., Liou Y.J., Tsai S.J. Impact of apolipoprotein A5 (APOA5) polymorphisms on serum triglyceride levels in schizophrenic patients under long-term atypical antipsychotic treatment // World J Biol Psychiatry. – 2012. – Jan. − Vol. 13, No. 1. – R. 22–29.

46. de Leon J., Correa JC, Ruaño G, Windemuth A, Arranz MJ, Diaz FJ. Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels // Schizophr Res. – 2008. – Jan. − Vol. 98, No. 1–3. – R. 40–46.

47. Diaz F.J., Meary A., Arranz M.J., Ruaño G., Windemuth A., de Leon J. Acetyl-coenzyme A carboxylase alpha gene variations may be associated with the direct effects of some antipsychotics on triglyceride levels // Schizophr Res. – 2009. – Dec. − Vol. 115, No. 2–3. – R. 136–140.

48. Smith R.C., Segman R.H., Golcer-Dubner T., Pavlov V., Lerer B. Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia // Pharmacogenomics J. – 2008. – Jun. − Vol. 8, No. 3. – R. 228–236.

49. Liou Y.J., Tsai S.J., Wang Y.C., Bai Y.M., Hong C.J. Genetic variants of microsomal triglyceride transfer protein (MTTP) are associated with metabolic syndrome in schizophrenic patients treated with atypical antipsychotics // J Clin Psychopharmacol. – 2013. – Jun. − Vol. 33, No. 3. – R. 313–318.

50. Lauressergues E., Bert E., Duriez P., Hum D., Majd Z., Staels B., Cussac D. Does endoplasmic reticulum stress participate in APD-induced hepatic metabolic dysregulation? // Neuropharmacology. – 2012. – Feb. − Vol. 62, No. 2. – R. 784–796.

51. Yang L., Chen J., Li Y., Wang Y., Liang S., Shi Y., Shi S., Xu Y. Association between SCAP and SREBF1 gene polymorphisms and metabolic syndrome in schizophrenia patients treated with atypical antipsychotics // World J Biol Psychiatry. – 2016. – Apr. − Vol. 28. – R. 1–8.

52. Ozasa R., Okada T., Nadanaka S., Nagamine T., Zyryanova A., Harding H., Ron D., Mori K. The antipsychotic olanzapine induces apoptosis in insulin-secreting pancreatic β cells by blocking PERK-mediated translational attenuation // Cell Struct Funct. – 2013. – Vol. 38, No. 2. – R. 183–195.

53. Ono S., Suzuki Y., Fukui N., Sugai T., Watanabe J., Tsuneyama N., Someya T. Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine // Pharmacogenomics J. – 2012. – Dec. − Vol. 12, No. 6. – R. 507–512.

54. Ono S., Suzuki Y., Fukui N., Sawamura K., Sugai T., Watanabe J., Tsuneyama N., Someya T. GIPR Gene polymorphism and weight gain in patients with schizophrenia treated with olanzapine // J Neuropsychiatry Clin Neurosci. – 2015. – Vol. 27, No. 2. – R. 162–164.

55. Brandl E.J., Tiwari A.K., Chowdhury N.I., Zai C.C., Lieberman J.A., Meltzer H.Y., Kennedy J.L., Müller D.J. Genetic variation in the GCG and in the GLP1R genes and antipsychotic-induced weight gain // Pharmacogenomics. – 2014. – Mar. − Vol. 15, No. 4. – R. 423–431.

56. Ramsey T.L., Liu Q., 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. – May. – Vol. 15, No. 7. – R. 933–939.

57. Brandl E.J., Tiwari A.K., Lett T.A., Shaikh S.A., Lieberman J.A., Meltzer H.Y., Kennedy J.L., Müller D.J. Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain // Hum Psychopharmacol. – 2013. – Mar. − Vol. 28, No. 2. – R. 183–187.

58. Ruaño G., Goethe J.W., Caley C., Woolley S., Holford T.R., Kocherla M., Windemuth A., de Leon J. Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients // Mol Psychiatry. – 2007. – May. − Vol. 12, No. 5. – R. 474–482.

59. Gaysinskaya V.A., Karatayev O., Chang G.Q., Leibowitz S.F. Increased Caloric Intake after a High-Fat Preload: Relation to Circulating Triglycerides and Orexigenic Peptides // Physiol Behav. – 2007. – Vol. 91. – R. 142–153.

60. Rossi A., Cañas F., Fagiolini A., Larmo I., Levy P., Montes J.M., Papageorgiou G., Sturlason R., Zink M., Correll C.U. Switching among antipsychotics in everyday clinical practice: Focus on ziprasidone // Postgraduate Medicine. – 2011. – Vol. 123. – R. 135−159.

61. Weiden P.J., Daniel D.G., Simpson G., Romano S.J. Improvement in indices of health status in outpatients with schizophrenia switched to ziprasidone // J of Clinical Psychopharmacology. – 2000. – Vol. 23. – R. 595–600.

62. Sárvári A.K., Veréb Z., Uray I.P., Fésüs L., Balajthy Z. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro // Biochem Biophys. Res Commun. – 2014. – Aug. 8. – Vol. 450, No. 4. – R. 1383–1389.

63. Swathy B., Banerjee M. Understanding epigenetics of schizophrenia in the backdrop of its antipsychotic drug therapy // Epigenomics. – 2017. – May. – Vol. 9, No. 5. – R. 721–736.