Metabolomics Mapping Changed After Olanzapine Therapy in Drug-naive Schizophrenia Patients-the Significant Impact of Gene Polymorphisms

Overview

Journal Toxicol Res (Camb)

Publisher Oxford University Press

Date 2022 Jul 5

PMID 35782649

Authors

Bensu Karahalil

Aylin Elkama

Mehmet Ak

Emirhan Nemutlu

Affiliations

Soon will be listed here.

Abstract

Oxidative stress may contribute to the development of schizophrenia and antipsychotics used in schizophrenia treatment may also cause oxidative stress. Gene polymorphisms on antioxidant and repair enzymes are responsible for individual variations and may change the efficacy of olanzapine treatment among schizophrenia patients. In our study, we assessed oxidative stress-related metabolite changes due to genetic polymorphisms on first diagnosed-schizophrenia patients treated with olanzapine. Blood samples ( = 30 patients) were taken before treatment (T1), after 10 ± 1 days (T2), and after 3 ± 1 months (T3). T1 served as control for T2 and T3, since it is advantageous to perform on same patient to evaluate the impact of olanzapine only. (, , and ) and gene polymorphisms were analyzed by polymerase chain reaction. Changes in metabolites were detected with metabolomics profiling by gas chromatography-mass spectrometry according to each genotype before and after treatment. Multivariate analysis showed that metabolomics profiles differed after olanzapine treatment regardless gene polymorphisms. Tryptophan could be a biomarker in response to olanzapine treatment since its levels were increased after treatment. gene polymorphism caused significant changes in some metabolites after treatment. Urea, palmitic acid, and caprylic acid levels increased and alanine levels decreased in patients with genotypes after olanzapine. In future, targeted metabolomics with these prominent metabolites and assessing gene expressions of will be beneficial to understand the mechanism of action.

Citing Articles

Are changes in olanzapine-induced liver enzyme levels associated with , , , and gene polymorphisms?.

Elkama A, Ilik N, Ak M, Karahalil B Arh Hig Rada Toksikol. 2024; 75(1):61-67.

PMID: 38548381 PMC: 10978158. DOI: 10.2478/aiht-2024-75-3770.

References

Tamminga C, Holcomb H . Phenotype of schizophrenia: a review and formulation. Mol Psychiatry. 2004; 10(1):27-39. DOI: 10.1038/sj.mp.4001563. View

McEvoy J, Baillie R, Zhu H, Buckley P, Keshavan M, Nasrallah H . Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics. PLoS One. 2013; 8(7):e68717. PMC: 3722141. DOI: 10.1371/journal.pone.0068717. View

Carta G, Murru E, Banni S, Manca C . Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications. Front Physiol. 2017; 8:902. PMC: 5682332. DOI: 10.3389/fphys.2017.00902. View

Gawryluk J, Wang J, Andreazza A, Shao L, Yatham L, Young L . Prefrontal cortex glutathione S-transferase levels in patients with bipolar disorder, major depression and schizophrenia. Int J Neuropsychopharmacol. 2011; 14(8):1069-74. DOI: 10.1017/S1461145711000617. View

Boskovic M, Vovk T, Kores Plesnicar B, Grabnar I . Oxidative stress in schizophrenia. Curr Neuropharmacol. 2011; 9(2):301-12. PMC: 3131721. DOI: 10.2174/157015911795596595. View

Saruwatari J, Yasui-Furukori N, Kamihashi R, Yoshimori Y, Oniki K, Tsuchimine S . Possible associations between antioxidant enzyme polymorphisms and metabolic abnormalities in patients with schizophrenia. Neuropsychiatr Dis Treat. 2013; 9:1683-98. PMC: 3818100. DOI: 10.2147/NDT.S52585. View

Clish C . Metabolomics: an emerging but powerful tool for precision medicine. Cold Spring Harb Mol Case Stud. 2016; 1(1):a000588. PMC: 4850886. DOI: 10.1101/mcs.a000588. View

Kim S, Kang S, Chung J, Park H, Cho K, Park M . Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis. Int J Mol Sci. 2015; 16(8):19602-11. PMC: 4581314. DOI: 10.3390/ijms160819602. View

Martins M, Petronilho F, Gomes K, Dal-Pizzol F, Streck E, Quevedo J . Antipsychotic-induced oxidative stress in rat brain. Neurotox Res. 2008; 13(1):63-9. DOI: 10.1007/BF03033368. View

10.

Atasoy N, Erdogan A, Yalug I, Ozturk U, Konuk N, Atik L . A review of liver function tests during treatment with atypical antipsychotic drugs: a chart review study. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(6):1255-60. DOI: 10.1016/j.pnpbp.2007.05.005. View

11.

Alfredsson G, Wiesel F . Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients. Psychopharmacology (Berl). 1990; 101(3):324-31. DOI: 10.1007/BF02244049. View

12.

Gonul N, Kadioglu E, Kocabas N, Ozkaya M, Karakaya A, Karahalil B . The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population. Gene. 2012; 505(1):121-7. DOI: 10.1016/j.gene.2012.05.025. View

13.

Bjerkenstedt L, Edman G, Hagenfeldt L, Sedvall G, Wiesel F . Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls. Br J Psychiatry. 1985; 147:276-82. DOI: 10.1192/bjp.147.3.276. View

14.

Ozcan O, Ipcioglu O, Gultepe M, Basogglu C . Altered red cell membrane compositions related to functional vitamin B(12) deficiency manifested by elevated urine methylmalonic acid concentrations in patients with schizophrenia. Ann Clin Biochem. 2008; 45(Pt 1):44-9. DOI: 10.1258/acb.2007.007057. View

15.

Kaddurah-Daouk R, McEvoy J, Baillie R, Lee D, Yao J, Doraiswamy P . Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Mol Psychiatry. 2007; 12(10):934-45. DOI: 10.1038/sj.mp.4002000. View

16.

Van Winkle E . The toxic mind: the biology of mental illness and violence. Med Hypotheses. 2000; 54(1):146-56. DOI: 10.1054/mehy.1998.0834. View

17.

Yan C, Duan L, Fu C, Tian C, Zhang B, Shao X . Association Between Glutathione S-Transferase (GST) Polymorphisms and Schizophrenia in a Chinese Han Population. Neuropsychiatr Dis Treat. 2020; 16:479-487. PMC: 7038391. DOI: 10.2147/NDT.S235043. View

18.

Chiappelli J, Postolache T, Kochunov P, Rowland L, Wijtenburg S, Shukla D . Tryptophan Metabolism and White Matter Integrity in Schizophrenia. Neuropsychopharmacology. 2016; 41(10):2587-95. PMC: 4987857. DOI: 10.1038/npp.2016.66. View

19.

Gardner D, Baldessarini R, Waraich P . Modern antipsychotic drugs: a critical overview. CMAJ. 2005; 172(13):1703-11. PMC: 1150265. DOI: 10.1503/cmaj.1041064. View

20.

Xuan J, Pan G, Qiu Y, Yang L, Su M, Liu Y . Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action. J Proteome Res. 2011; 10(12):5433-43. DOI: 10.1021/pr2006796. View