8-hydroxy-2--deoxyguanosine and Depressive-Disorder

Previous studies have indicated that antidepressants that inhibit the serotonin transporter reduces oxidative stress. DNA and RNA damage from oxidation is involved in aging and a range of age-related pathophysiological processes. Here, we studied the urinary excretion of markers of DNA and RNA damage from oxidation, 8-oxodG and 8-oxoGuo, respectively, in the NeuroPharm cohort of 100 drug-free patients with unipolar depression and in 856 non-psychiatric community controls. Patients were subsequently treated for 8 weeks with escitalopram in flexible doses of 5-20 mg; seven of these switched to duloxetine by week 4, as allowed by the protocol. At week 8, 82 patients were followed up clinically and with measurements of 8-oxodG/8-oxoGuo. Contextual data were collected in patients, including markers of cortisol excretion and low-grade inflammation. The intervention was associated with a substantial reduction in both 8-oxodG/8-oxoGuo excretion (25% and 10%, respectively). The change was not significantly correlated to measures of clinical improvement. Both markers were strongly and negatively correlated to cortisol, as measured by the area under the curve for the full-day salivary cortisol excretion. Surprisingly, patients had similar levels of 8-oxodG excretion and lower levels of 8-oxoGuo excretion at baseline compared to the controls. We conclude that intervention with serotonin reuptake inhibitors in unipolar depression is associated with a reduction in systemic DNA and RNA damage from oxidation. To our knowledge, this to date the largest intervention study to characterize this phenomenon, and the first to include a marker of RNA oxidation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Deoxyguanosine; Depressive Disorder; DNA; DNA Damage; Humans; Hydrocortisone; Oxidative Stress; RNA

Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders.. Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction.. At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index.. Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Bipolar Disorder; Depressive Disorder; DNA Glycosylases; Female; Gene Expression; Humans; Male; Oxidative Stress; Young Adult

This study investigated the connection among the oxidative stress, depression and expression of specific genes involved in DNA-damage signaling pathways in patients with colorectal carcinoma (CRC).. A unique Dukes'C subset of patients with newly diagnosed colorectal adenocarcinoma were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90) and other multiple-item questionnaires. Oxidative-stress-related parameters in sera and the expression of genes were monitored during a pretreatment period.. Eighty-two eligibility cases were divided into 2 groups based on an HAMD score cutoff of 20: the mean score was 28.29 in Group A (depression, n=52) and 16.50 in Group B (nondepression, n=30). The serum total antioxidant capacity, catalase, and superoxide dismutase concentrations were lower in Group A, whereas those of nitric oxide and malondialdehyde were higher in Group A. Importantly, the 8-hydroxy-deoxyguanosine level was higher in Group A than in Group B (P<.05). Microarray analysis revealed that the expressions of p34, PA26, and ABL were higher in Group A, whereas those of HRAD51, CR6, and XRCC3 were higher in Group B.. Oxidative stress is capable of causing neuronal toxicity via lipid peroxidation, DNA damage, and abnormalities of gene expression, and therefore is a possible pathogenic mechanism underlying depression in patients with CRC.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma; Adult; Aged; Colorectal Neoplasms; Depressive Disorder; DNA Damage; Female; Gene Expression Regulation, Neoplastic; Guanine; Humans; Male; Middle Aged; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Personality Inventory; Psychometrics; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Signal Transduction