Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent.

Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case-control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5'-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms.

The association of electroconvulsive therapy to pharmacological treatment and its influence on cytokines.

INTRODUCTION: A growing body of evidence shows that disturbances in the immune system are involved in the pathogenesis of depression. Although the immune-modulating effects of antidepressants have been described, few studies have addressed the functioning of the immune system in relation to electroconvulsive therapy (ECT). This study aims to investigate if the addition of ECT to pharmacotherapy is associated with changes in cytokine levels. METHODS: Adult inpatients were invited to participate in this study on admission to a psychiatric unit. Those with a diagnosis of depression by Mini-International Neuropsychiatric Interview were included. At treatment discharge, patients were retrospectively divided into those who used combined ECT and pharmacotherapy (31 subjects) and those who used only pharmacotherapy (68 subjects). Pro-inflammatory cytokines IL-2, IL-6, TNF-α, IFN-γ, and IL-17, and anti-inflammatory IL-4 and Il-10, were measured in blood samples collected at admission and discharge. A generalized estimating equation model and the post hoc Bonferroni test were performed for statistical analysis. RESULTS: The combination of ECT with pharmacotherapy was associated with a decrease of IL-6 and an increase of TNF-α. Depressive inpatients, as a whole group, had a decrease of IL-6 and an increase of IFN-γ. No significant results were found for IL-2, IL-4, Il-10 and IL-17. CONCLUSION: This study is clinically relevant because we highlight that, in agreement with the previous literature, IL-6 appears to be a useful marker in depression, and we show for the first time that its reduction is closely related to the use of ECT.

Remission of depression following electroconvulsive therapy (ECT) is associated with higher levels of brain-derived neurotrophic factor (BDNF).

INTRODUCTION: Research on the association between electroconvulsive therapy (ECT) and increased brain derived neurotrophic factor (BDNF) levels has produced conflicting result. There have been few studies which have evaluated BDNF levels in clinical contexts where there was remission following treatment. The objective of this study was to investigate whether remission of depression following ECT is associated with changes in BDNF levels. METHODS: Adult inpatients in a psychiatric unit were invited to participate in this naturalistic study. Diagnoses were made using the Mini-International Neuropsychiatric Interview (MINI) and symptoms were evaluated at admission and discharge using the Hamilton Rating Scale for Depression (HDRS-17). Thirty-one patients who received a diagnosis of depression and were subjected to ECT were included retrospectively. Clinical remission was defined as a score of less than eight on the HDRS-17 at discharge. Serum BDNF levels were measured in blood samples collected at admission and discharge with a commercial kit used in accordance with the manufacturer's instructions. RESULTS: Subjects HDRS-17 scores improved following ECT (t = 13.29; p = 0.00). A generalized estimating equation (GEE) model revealed a remission × time interaction with BDNF levels as a dependent variable in a Wald chi-square test [Wald χ(2) = 5.98; p = 0.01]. A post hoc Bonferroni test revealed that non-remitters had lower BDNF levels at admission than remitters (p = 0.03), but there was no difference at discharge (p = 0.16). CONCLUSION: ECT remitters had higher serum BDNF levels at admission and the level did not vary during treatment. ECT non-remitters had lower serum BDNF levels at admission, but levels increased during treatment and were similar to those of ECT remitters at discharge.

Combining ECT with pharmacological treatment of depressed inpatients in a naturalistic study is not associated with serum BDNF level increase.

BACKGROUND: BDNF blood levels are reduced in MDD. They can be increased with pharmacologic treatment and ECT, but it is not clear whether the combination of treatments promotes an additional increase. The present study aims to evaluate whether combined treatment promotes an increase in BDNF, restoring the level to that of non-depressed controls. METHODS: Ninety-nine adult inpatients were invited to participate in this naturalistic prospective cohort study between May 2011 and April 2013. Diagnosis was made by MINI, and the symptoms were evaluated at admission and at discharge by HDRS-17. Those inpatients with a diagnosis of depression were included and divided into two groups: those who underwent combined ECT and medication (31 subjects) and those who used only pharmacotherapy (68 subjects). Serum BDNF was measured in blood samples collected at admission and discharge. One hundred healthy blood donors without any psychiatric diagnosis were included as a control group. RESULTS: There were no significant differences in serum BDNF levels between the combined and pharmacological groups at admission and at discharge, and no significant variation in BDNF occurred in any group during the treatment. There were no interactions between time and treatment groups nor significant time effects or treatment group effects for BDNF in the Generalized Estimating Equation Model (GEE). The control group had significantly higher serum BDNF levels in comparison with each of the treatment groups at admission and discharge (p = 0.00). CONCLUSION: Combination of ECT with pharmacological treatment did not result in increased serum BDNF levels and did not restore levels to that of controls.