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Yayın A comparative meta-analysis of peripheral 8-hydroxy-2?-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-Oxo-DG) levels across mood episodes in bipolar disorder(Wiley, 2023) Arat Çelik, H. E.; Tuna, Gamze; Ceylan, Deniz; Kucukgoncu, Suat[Abstract Not Available]Yayın A comparative meta-analysis of peripheral 8-hydroxy-2?-deoxyguanosine mood episodes in bipolar disorder(Pergamon-Elsevier Science Ltd, 2023) Arat Çelik, Hidayet Ece; Tuna, Gamze; Ceylan, Deniz; Kucukgoncu, SuatObjective: Oxidative DNA damage has been associated with the pathophysiology of bipolar disorder (BD) as one of the common pathways between increased medical comorbidity and premature aging in BD. Previous evidence shows increased levels of oxidatively induced DNA damage markers, 8-hydroxy-2 '-deoxyguanosine (8-OHdG) or its tautomer 8-oxo-7,8-dihydro-2 '-deoxyguanosine (8-oxo-dG), in patients with BD in comparison to healthy individuals. With the current research, we aim to analyze data on peripheral (blood or urine) 8-OHdG/8-oxo-dG levels across mood states of BD using a meta-analytical approach.Method: A literature search was conducted using the databases PubMed, Scopus, and Web of Science to identify eligible studies (January 1989 to July 2022). Relevant studies were systematically reviewed; a random-effects meta-analysis and a meta-regression analysis were conducted.Results: The current meta-analysis included 12 studies consisting of 808 BD patients (390 in euthymia, 156 in mania, 137 in depression, 16 in mixed episode, 109 not specified) and 563 healthy controls. BD patients that were currently depressed had significantly higher levels of 8-OHdG/8-oxo-dG than healthy controls, while euthymic or manic patients did not differ from healthy controls. A meta-regression analysis showed sex distri-bution (being female) and older age to be significantly related to increased 8-OHdG/8-oxo-dG levels.Conclusion: Our findings suggest that 8-OHdG/8-oxo-dG may be a state-related marker of depression in BD and may be affected by older age and female gender.Yayın Integrating mitoepigenetics into research in mood disorders: a state-of-the-art review(Frontiers Media Sa, 2024) Ceylan, Deniz; Arat-Çelik, Hidayet Ece; AkŞahin, Izel CemreMood disorders, including major depressive disorder and bipolar disorder, are highly prevalent and stand among the leading causes of disability. Despite the largely elusive nature of the molecular mechanisms underpinning these disorders, two pivotal contributors-mitochondrial dysfunctions and epigenetic alterations-have emerged as significant players in their pathogenesis. This state-of-the-art review aims to present existing data on epigenetic alterations in the mitochondrial genome in mood disorders, laying the groundwork for future research into their pathogenesis. Associations between abnormalities in mitochondrial function and mood disorders have been observed, with evidence pointing to notable changes in mitochondrial DNA (mtDNA). These changes encompass variations in copy number and oxidative damage. However, information on additional epigenetic alterations in the mitochondrial genome remains limited. Recent studies have delved into alterations in mtDNA and regulations in the mitochondrial genome, giving rise to the burgeoning field of mitochondrial epigenetics. Mitochondrial epigenetics encompasses three main categories of modifications: mtDNA methylation/hydroxymethylation, modifications of mitochondrial nucleoids, and mitochondrial RNA alterations. The epigenetic modulation of mitochondrial nucleoids, lacking histones, may impact mtDNA function. Additionally, mitochondrial RNAs, including non-coding RNAs, present a complex landscape influencing interactions between the mitochondria and the nucleus. The exploration of mitochondrial epigenetics offers valuable perspectives on how these alterations impact neurodegenerative diseases, presenting an intriguing avenue for research on mood disorders. Investigations into post-translational modifications and the role of mitochondrial non-coding RNAs hold promise to unravel the dynamics of mitoepigenetics in mood disorders, providing crucial insights for future therapeutic interventions.Yayın Neurocognitive Functions in Bipolar Disorder in Relation to Comorbid ADHD(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2021) Arat Çelik, Hidayet Ece; Ceylan, Deniz; Hidiroğlu Ongun, Ceren; Erdoğan, Ayşe; Tan, Devran; Gumuskesen, Peren; Bagci, BasakIntroduction: Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) often co-occur in adult population. Both conditions present various neurocognitive and behavioral problems. We aimed to examine neurocognitive functions in adult patients with comorbid BD and ADHD (BD+ADHD) in comparison to patients with only BD, only ADHD and healthy controls (HCs). Method: An extensive cognitive battery which evaluates verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency, was used to assess neurocognitive functions respectively in adult (age 18-65 years) patients with BD (n=37), ADHD (n=43), BD+ADHD (n=20) in comparison to HCs (n=51). The Multivariate Analysis of Covariance models, where age, level of education and total BIS-11 scores were included as covariates, were used for comparing neurocognitive scores among groups. Results: Both BD and BD+ADHD groups showed significantly poorer performance than HCs in processing speed, attention, executive functions, and verbal fluency domains. The BD group had additional significant deficits in executive functions, verbal learning and memory domains. There were no significant differences between BD and BD+ADHD groups with regards to verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency domains. Patients with only ADHD showed significantly poorer performance than HCs in verbal fluency domain. Conclusions: Our results show similarities in the neurocognitive functions of adults with BD and BD+ADHD across a wide range of cognitive domains. The findings point to the need for further exploration of diverging and converging neurodevelopmental trajectories of BD and ADHD.Yayın Oxidative DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder(Research Square, 2023) Çelik, Hidayet Ece; Yılmaz, Seda; Kendirlioğlu, Burcu Kök; Çörekli, Esma; Bekar, Nazlı Dal; Çelik, Ömer; Yorguner, Neşe; Öztürk, Bilge Targıtay; İşlekel, Hüray; Özerdem, Ayşegül; Akan, Pınar; Ceylan, Deniz; Tuna, GamzePrevious evidence suggests elevated levels of oxidative DNA damage, particularly 8-hydroxy-2'- deoxyguanosine (8-OH-dG), and abnormalities in the repair of 8-OH-dG by the base excision repair (BER) in BD. However, the genetic disposition of these abnormalities remains unknown. In this study, we aimed to investigate the levels of oxidative DNA damage and BER mechanisms in individuals with BD and their siblings, as compared to healthy controls (HCs). 46 individuals with BD, 41 siblings of individuals with BD, and 51 HCs were included in the study. Liquid chromatography-tandem mass spectrometry was employed to evaluate the levels of 8-OH-dG in urine, which were then normalized based on urine creatinine levels. The real-time-polymerase chain reaction was used to measure the expression levels of 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), poly ADP-ribose polymerase 1 (PARP1), and DNA polymerase beta (POL?). The levels of 8-OH-dG were found to be elevated in both individuals with BD and their siblings when compared to the HCs. The OGG1 and APE1 expressions were downregulated, while POL? expressions were upregulated in both the patient and sibling groups compared to the HCs. Age, smoking status, and the number of depressive episodes had an impact on APE1 expression levels in the patient group while body mass index, smoking status, and past psychiatric history had an impact on 8-OH-dG levels in siblings. Both individuals with BD and unaffected siblings presented similar abnormalities regarding oxidative DNA damage and BER, suggesting a link between abnormalities in DNA damage / BER mechanisms and familial susceptibility to BD. Our findings suggest that targeting the oxidative DNA damage and BER pathway could offer promising therapeutic strategies for reducing the risk of age-related diseases and comorbidities in individuals with a genetic predisposition to BD.Yayın Quality of Life of Individuals with Bipolar Disorder and Schizophrenia(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2022) Çelik, Hidayet Ece Arat; Ceylan, Deniz; Bagci, Basak; Akdede, Berna Binnur; Alptekin, Koksal; Özerdem, AyşegülIntroduction: Quality of life (QoL) is a concept defined as a subjective perception of one's position in life and is negatively affected in many psychiatric illnesses such as bipolar disorder (BD) and schizophrenia (SCZ). It is hypothesized that therapeutic approaches based on QoL can increase the patient's adherence to treatment and contribute to a satisfactory life. This study aimed to compare the QoL of individuals having BD and schizophrenia with that of healthy controls (HCs) and to investigate the impact of the state of remission on QoL.Method: The World Health Organization QoL Scale-Short Form (WHOQOL-Bref) was administered to individuals with BD (n=124) and SCZ (n=74) and to HCs (n=81) to evaluate QoL. The WHOQOL-Bref subscale and total scores were compared between the groups using multifactor analysis of covariance (MANCOVA) by considering age and education level as the covariates. Then, the patient groups were compared using MANCOVA based on the state of remission by taking age, level of education, and Global Assessment of Functioning scores as the covariates. The relationship between clinical features and QoL scores was evaluated using correlation analysis, and linear regression analysis was applied for the variables that were found to be significant.Results: It was found that individuals with SCZ or BD had lower WHOQOL-Bref psychological, social, and total scores than HCs. Those with SCZ additionally had lower physical and environmental subscale scores than HCs. Furthermore, those with SCZ had lower WHOQOL-Bref physical, psychological, social, and total scores than individuals with BD. There was no significant difference in WHOQOL-Bref scores between individuals with BD and SCZ in the remission period. WHOQOL-Bref physical, psychological, and total scores were found to be significantly lower in unremitted BD patients when compared with remitted BD patients. Unremitted BD patients were found to have significantly lower WHOQOL-Bref psychological, environmental, and total scale scores than unremitted SCZ patients. Conclusion: It can be concluded that the QoL of individuals with BD is between that of healthy individuals and those with SCZ. However, unremitted BD patients have lower QoL than unremitted SCZ patients. Both patient groups display similar features during remission. Identifying the similarities and differences in terms of QoL in both patient groups is of great importance to develop the best type of treatment for the patients.Yayın Use of smartphone applications in the follow-up of individuals with bipolar disorder: psychiatrists' opinions and concerns(Wiley, 2022) Gurcan, A.; Çelik, Hidayet Ece; Alici, Yasemin Hoşgören; Bagcaz, Arda; Ercis, Mete; Ceylan, Deniz[Abstract Not Available]
