Depression Treatment: Pharmacogenetics of Efficacy and Safety of HCV Treatment in HCV-HIV Coinfected Patients: Significant Associations With IL28B and SOCS3 Gene Variants.

Pharmacogenetics of Efficacy and Safety of HCV Treatment in HCV-HIV Coinfected Patients: Significant Associations with IL28B and SOCS3 Gene Variants.

Filed under: Depression Treatment

PLoS One. 2012; 7(11): e47725
Vidal F, López-Dupla M, Laguno M, Veloso S, Mallolas J, Murillas J, Cifuentes C, Gallart L, Auguet T, Sampériz G, Payeras A, Hernandez P, Arnedo M, Gatell JM, Richart C

This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFN?) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients.The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNF?, IFN?, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student’s T test, Mann-Whitney U test and logistic regression were used for statistic analyses.As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p?=?0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p?=?0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p?=?0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p?=?0.049 and p?=?0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p?=?0.02 and p?=?0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p?=?0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p?=?0.01) remained significant.In HCV-HIV coinfected patients treated with PegIFN? and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism. HubMed – depression


Depressive Symptoms Are Not Associated with Leukocyte Telomere Length: Findings from the Nova Scotia Health Survey (NSHS95), a Population-Based Study.

Filed under: Depression Treatment

PLoS One. 2012; 7(10): e48318
Shaffer JA, Epel E, Kang MS, Ye S, Schwartz JE, Davidson KW, Kirkland S, Honig LS, Shimbo D

Premature shortening of leukocyte telomere length has been proposed as a novel mechanism by which depression may confer increased risk of adverse cardiovascular events. Prior studies demonstrating associations of depression and depressive symptoms with shorter leukocyte telomere length were small, included selected psychiatric outpatients, were based on convenience samples, and/or adjusted for a limited number of possible confounding factors.We examined the associations of depressive symptoms, probable depressive disorder, and specific depressive symptom clusters, as assessed by the Center for Epidemiological Studies-Depression (CES-D) scale, with leukocyte telomere length, measured by using a real-time PCR method, in 2,225 apparently healthy participants from the 1995 Nova Scotia Health Survey population-based study. The mean age was 48.2±18.9 years; 49.9% of participants were female; and the mean CES-D score was 7.4±7.9. The mean telomere length was 5,301±587 base pairs. In an unadjusted model, depressive symptoms were significantly associated with longer leukocyte telomere length (B?=?27.6 base pairs per standard deviation increase in CES-D, 95% confidence interval [CI]?=?3.1-52.1, p?=?0.027). This association was no longer significant after adjustment for age and sex (B?=?9.5, 95% CI?=?-14.6-33.6, p?=?0.44) or after further adjustment for body mass index, Framingham risk score and previous history of ischemic heart disease (all p’s?0.37). Neither probable depressive disorder nor specific depressive symptom clusters were independently associated with leukocyte telomere length.Concurrent depressive symptoms were not associated with leukocyte telomere length in a large, representative, population-based study.
HubMed – depression


Mortality and suicide risk in treatment-resistant depression: an observational study of the long-term impact of intervention.

Filed under: Depression Treatment

PLoS One. 2012; 7(10): e48002
Olin B, Jayewardene AK, Bunker M, Moreno F

Major depressive disorder is a common global disease that causes a significant societal burden. Most interventional studies of depression provide a limited assessment of the interventions on mortality and suicide risks. This study utilizes data from an observational registry of patients with major depressive disorder to determine the impact of intervention (vagus nerve stimulation or standard pharmacological/non-pharmacological therapy) and a latent factor, patient trajectory toward response, on mortality, suicide and suicidal ideation. A total of 636 patients were available for an intent-to-treat analysis of all-cause mortality, suicide and suicidal ideation. Patients treated with vagus nerve stimulation in addition to standard therapies experienced lower, but not statistically significant, all-cause mortality (vagus nerve stimulation 4.93 per 1,000 person-years vs. 10.02 per 1,000 patient years for treatment as usual) and suicide rates (vagus nerve stimulation 0.88 per 1,000 person-years vs. 1.61 per 1,000 patient years for treatment as usual). Treatment with vagus nerve stimulation produced a statistically lower relative risk of suicidal ideation 0.80, 95% confidence interval (0.68,0.95). Further, patients that responded to either treatment saw a 51% reduction in relative risk of suicidal behavior; relative risk and 95% confidence interval of 0.49 (0.41,0.58). In summary, we find that treatment with adjunctive vagus nerve stimulation can potentially lower the risk of all-cause mortality, suicide and suicide attempts.
HubMed – depression



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