The Toxicity Potential of Antidepressants and Antipsychotics in Relation to Other Medication and Alcohol: A Naturalistic and Retrospective Study.

QT interval prolongation and ventricular tachyarrhythmia are potential adverse effects of antidepressant (AD) and antipsychotic- (AP) agents, especially when overdosed. Since AD and AP agents are often prescribed to patients suffering from suicidal intentions, it is essential to estimate these risks in the context of intoxications. This retrospective and naturalistic one-year registry study included 105 patients treated for oral intoxication at the University Department of Emergency Medicine in Vienna, Austria. AD/AP intoxications were present in 26 patients, while in the control group (n = 79) non-AD/AP drugs (n = 54) and exclusively alcohol (n = 25) were the toxic agents. QT intervals, the necessity of intubation, the extent of conscious state, and the subsequent discharge management were compared. The mean age was 34.94 ± 14.6 years, 62 patients (59%) were female. There were no significant between-group differences regarding QT prolongation >470 ms using Bazett's correction (p = 0.178), or >440 ms using Fridericia's correction (p = 0.760). No significant group differences concerning the need for intubation were observed (p = 0.747). The AD/AP and the control group did not significantly differ regarding Glasgow Coma Scale scores (p = 0.439). Patients with AD/AP intoxication were significantly more often transferred to the psychiatric department, while discharge to home was more likely in the control group (p = 0.002). These results suggest that the risk of a potentially life-threatening outcome in cases of intoxication with AD/AP is not substantially higher than in other easily available toxic agents, in line with the advantageous risk/benefit ratio of newer ADs and APs.

Oxytocin receptor gene methylation as a molecular marker for severity of depressive symptoms in affective disorder patients.

BACKGROUND: Oxytocin (OXT) is a neuropeptide and hormone involved in emotional functioning and also seems to play a role in moderating the stress response. Both preclinical and clinical studies point to an increased methylation status of the Oxytocin receptor (OXTR) promoter region with concomitant deficits in social, cognitive and emotional functioning. We hypothesize that methylation levels (%) of the oxytocin receptor promoter region correlate with the severity of depression symptoms and/or with the severity of childhood trauma within this present sample of affective disorder patients. METHODOLOGY: Eight hundred forty six (846) affective disorder patients of Central European origin were recruited at the Department of Psychiatry and Psychotherapy of the Medical University Vienna, the Karl Landsteiner University for Health and Science and Zentren für seelische Gesundheit, BBRZ-Med Leopoldau. Psychiatric assessment included a semi-structured diagnostic interview (Schedules for Clinical Assessment in Neuropsychiatry), the Hamilton Depression Scale and the Childhood Trauma Questionnaire. Concomitantly DNA samples of peripheral blood cells were collected for Multiplexed and Sensitive DNA Methylation Testing. RESULTS: Our data suggests a positive but not significant association between OXTR promoter Exons 1-3 methylation levels and severity of depression symptoms as well as severity of emotional neglect in affective disorder patients and no association with childhood trauma. CONCLUSIONS: Our findings contribute to elucidate the role of OXTR in affective disorders, but further longitudinal studies in particular are necessary to broaden the current state of knowledge.

BDNF gene polymorphisms predicting treatment response to CBT-based rehabilitation of depression: to be submitted to: European Neuropsychopharmacology.

Genetic factors were shown to play a major role in both variation of treatment response and incidence of adverse effects to medication in affective disorders. Nevertheless, there is still a lack of therapygenetic studies, investigating the prediction of psychological therapy outcomes from genetic markers. Neuroplasticity and one of its mediators, brain-derived neurotrophic factor (BDNF), are potential research targets in this field. We aimed to investigate Tag SNP polymorphisms of the BDNF gene in depressed patients treated with cognitive behavioral therapy (CBT) in the context of a standardized 6-weeks outpatient rehabilitation program. Treatment response was assessed calculating the mean differences in BDI-II (Beck Depression Inventory) scores from admission to discharge. Six BDNF SNPs, including the Val66Met polymorphism (rs6265), were genotyped. Both genotypic data and BDI-II-scores at admission and discharge were available for 277 patients. Three SNPs, rs10501087 (p = 0.005, FDRp=0.015), rs11030104 (p = 0.006, FDRp=0.012), and the Val66Met polymorphism (rs6265, p<0.001, FDRp=0.006), were significantly associated with treatment response in depressed patients, even after multiple testing correction using the false discovery rate method (FDRp). We conclude that BDNF might serve as promising genetic marker for treatment response to psychological treatment in depression. However, due to our limited sample size, further studies are needed to disentangle the role of BDNF as potential therapygenetic marker.