DETERMINATION OF POSSIBLE GENOTOXIC DAMAGE IN PATIENTS UNDER TREATMENT DUE TO DEPRESSION AND ANXIETY DISORDERS


Thesis Type: Doctorate

Institution Of The Thesis: Gazi University, Fen Bilimleri Enstitüsü, Turkey

Approval Date: 2022

Thesis Language: Turkish

Student: SALİH ÖZDEN

Supervisor: Deniz Yüzbaşıoğlu

Abstract:

Nowadays depression and anxiety are very common disorders that often seen together. In this study, four different genotoxicity tests (chromosomal aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), comet tests) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the possible genotoxic damage in patients with depression and anxiety disorder under therapy. Forty-seven patients who were diagnosed with depression and anxiety disorders according to the Diagnostic and Statistical Manual of Mental Diseases (DSM IV) diagnostic criteria and received pharmacological treatment (selective serotonin-reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors-SNRIs, and antipsychotics) were included in the study. In this study, no statsitically significant difference in both MN and SCE frequencies was found between the patient and the control groups. Also twenty-eight healthy volunteers were selected as a control group. As a result of the study, MN and SCE frequencies were not different significantly between the patient and the control groups. In CA and comet tests, it was determined that the patient group had statistically significantly higher DNA damage and CA frequency compared to the control group. There was no significant difference between the patient and the control groups in terms of mitotic (MI), replication (RI), and nuclear division (NDI) indices. When the patient group and the control group were compared, it was found that there was no significant relationship in the expression of investigated genes (bcl-2, hoxa13, hoxb13 and cyp1A1). However, hoxa13 gene expression was found to be significantly higher in patients who used single or combined fluoxetine compared to patients who did not use fluoxetine. In addition, it was found that the frequency of SCE was higher in patients with the initial diagnosis compared to the group of patients with recurrent diagnoses. When patients under monotherapy and combined treatment were compared, DNA damage was higher in patients used a single medication. Furthermore, it was determined that factors such as age, gender, initial or recurrent diagnosis, SNRI or SSRI use, combined therapy or monotherapy, and fluoxetine use did not cause a significant difference in the patient group. This study showed that depression and anxiety disease and/or treatment of the disease may constitute a risk factor for genetic according to the results of the CA and comet tests. It is thought that detailed results may be obtained by performing genotoxicity assessment of the patient group before and after treatment. 

Key Words : Depression, anxiety, genotoxicity, micronucleus, sister chromatid exchange, chromosomal aberration, comet, RT-qPCR