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    CYB mtDNA mutations and expression status of genes in the PI3K/AKT/mTOR signaling pathway in patients with schizophrenia
    (Cukurova Univ, Fac Medicine, 2022) Dirican, Ebubekir; Uzuncakmak, Sevgi Karabulut; Ozcan, Halil
    Purpose: This study aimed to screen for cytochrome b (CYB) mitochondrial DNA (mtDNA) mutations and analyze the mRNA expressions of genes in the PI3K/AKT/mTOR signaling pathway in patients with schizophrenia. Materials and Methods: In this study, whole blood was obtained from 44 schizophrenic patients and 41 healthy individuals for DNA (patients) and RNA (patients and control) isolation. Samples for CYB mtDNA mutations were amplified by PCR and identified by Sanger DNA sequencing. RT-PCR and 2- increment increment Ct method was used for mRNA expression of PIK3CA, AKT1, and mTOR genes. Results: In schizophrenia patients, m.15326 A > G (43/44), m.15452 C > A (5/44), m.15078 A > G (3/44), m.14872 C > T (3/44) and m.14798 T > C (3/44) was the most common CYB mtDNA mutations. In silico analysis showed that some of the mutations were associated with the harmful, disease-causing or benign character. The mRNA expression of the PIK3CA, AKT1, and mTOR genes in schizophrenia patients was significantly higher than in healthy individuals. There was a significant moderate positive correlation between the PIK3CA and AKT1 genes. In addition, by ROC analysis, PIK3CA, AKT1 and mTOR genes were found to have good diagnostic power in the patient group. ROC analyzes showed that PIK3CA in particular has significant diagnostic value for schizophrenia patients with 80% sensitivity and 63.4% specificity. Conclusion: Both of CYB mtDNA mutations frequency and PIK3CA, AKT1 and mTOR mRNA expression were higher in schizophrenic patients compared to healthy individuals. We believe that studying these mechanisms in
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    Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients
    (Korean Coll Neuropsychopharmacology, 2023) Dirican, Ebubekir; Ozcan, Halil; Uzuncakmak, Sevgi Karabulut; Takim, Ugur
    Objective: Apoptosis is programmed cell death that occurs by several pathways. Caspase-3 is induced by active caspase-9 via the intrinsic pathway. The aim of this research was to explore the expression of caspase-3 and caspase-9 in schizophrenia patients and healthy samples. Methods: RNA was isolated from the peripheral blood of 39 schizophrenia patients' and healthy samples. After cDNA synthesis, real time PCR (RT-PCR) was used to analyse caspase-3 and caspase-9 gene expression. The severity of psychopathological symptoms of schizophrenia was evaluated using the Positive and Negative Symptoms Scale for schizophrenia (PANSS) and Clinical Global Impressions (CGI). Results: The expression of caspase-3 and caspase-9 genes was higher in schizophrenia patients than in healthy samples (p = 0.012, p = 0.002, respectively). The increase in caspase-3 gene expression was significant with being male, smoking and with a duration of less than 6 years (p = 0.047, p = 0.049, p = 0.034, respectively). On the other hand, the increase in caspase-9 gene expression was significant in patients who is smoke, have children, and are under 33 years old (p = 0.040, p = 0.043, p = 0.045, respectively). A significant positive correlation was detected between the caspase-3 and caspase-9 gene expression (r = 0.3218, p = 0.049). Conclusion: Our findings indicate that caspase-3 and caspase-9 gene expression may activate cell death mechanisms by intrinsic apoptotic genes. Furthermore, caspase-3 and caspase-9 may play essential roles in different ways in schizophrenia. Hence there is a need to further study the apoptotic mechanism with expanded patient populations.
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    Relation of ATPase6 Mutations and Telomere Length in Schizophrenia Patients
    (Korean Coll Neuropsychopharmacology, 2023) Uzuncakmak, Sevgi Karabulut; Dirican, Ebubekir; Ozcan, Halil; Takim, Ugur
    Objective: Schizophrenia is a serious mental disorder. Mutations in mitochondrial genes can change energy metabolism. Telomere is a tandem sequence at the end of chromosomes. Shorter telomere length has been shown in schizophrenia. The aim of this study was to determine the relationship between ATPase6 gene mutations and telomere length in schizo-phrenia patients.Methods: Blood samples of 34 patients and 34 healthy controls were used. In this study conventional PCR, Sanger sequencing technic and real-time PCR were utilized.Results: Five different mutations (A8860G, A8836, G8697A, C8676T, and A8701G) in the ATPase6 gene were identified in schizophrenia patients. The most seen mutation was A8860G (94%). Telomere length analysis indicated the relation of ATPase6 gene mutations and telomere length variations (p = 0.001). Patients carrying the A8860G mutation had shorter telomere lengths than patients carrying other mutations. Comparing telomere length between schizophrenia pa-tients and healthy controls revealed that the mean telomere length of schizophrenia patients was shorter than healthy controls (p = 0.006). The demographic analysis demonstrated a significant relationship between marital status and telo-mere length (p = 0.011). Besides that, the duration of the illness is another factor that impacts telomere length (p = 0.044). There is no significant relation between telomere length and other clinical and demographic characteristics including education status, age, gender, etc.Conclusion: In conclusion, telomere length and ATPase6 gene mutations have a significant relation. Studies with larger patient populations and investigation of other mitochondrial gene mutations will make the clearer link between telomere length and mitochondrial mutations.