Metabolomics mapping changed after olanzapine therapy in drug-naive schizophrenia patients-the significant impact of gene polymorphisms
Küçük Resim Yok
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Oxford Univ Press
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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 (n = 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. GSTs (GSTM1, GSTT1, and GSTP1) and OGG1 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. GSTM1 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 GSTM1 null genotypes after olanzapine. In future, targeted metabolomics with these prominent metabolites and assessing gene expressions of GSTs will be beneficial to understand the mechanism of action.
Açıklama
Anahtar Kelimeler
Olanzapine, Metabolomics, Individual Susceptibility, Gene Polymorphism, Glutathione-S-Transferases
Kaynak
Toxicology Research
WoS Q Değeri
Q4
Scopus Q Değeri
Q3
Cilt
11
Sayı
3
