Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trial

Background: Low n-3 polyunsaturated fatty acids (PUFAs) has been linked to depression, but the preventive effect of n-3PUFAs supplementation on maternal depression needs further investigation. We aimed to evaluate the efficacy of a daily dose of n-3 PUFAs supplementation (fish oil) on the prevention of postpartum depression (PPD). Methods: A randomized, placebo-controlled, double blind trial was designed and nested into a cohort study conducted in Rio de Janeiro, Brazil. Sixty pregnant women identified as being at risk for PPD were invited and randomly assigned to receive fish oil capsules [1.8 g (1.08 g of Eicosapentaenoic (EPA) and 0.72 g of Docosapentaenoic (DHA) acids)] or placebo (control). The Edinburgh Postnatal Depression Scale (EPDS) was scored at 5–13 (T0, baseline), 22–24 (T1), 30–32 weeks of gestation (T2) and 4–6 weeks’ postpartum (T3). Supplementation started at week 22–24 of gestation (T1) and lasted for 16 weeks. Serum fatty acids were assayed to evaluate compliance. Prevalence of EPDS ≥11 was the primary outcome, and mean and changes in EPDS score, length of gestation, and birth weight the secondary outcomes. Linear mixed-effect (LME) and random-intercept logistic regression models were performed to test the effect of fish oil supplementation on prevalence of EPDS ≥11 and EPDS scores variation. Results: In intention-to-treat (ITT) analysis, at 30–32 weeks’ gestation women in the fish oil presented higher serum concentration of EPA, DHA and lower n-6/n-3 ratio comparing to the control group. There were no differences between intervention and control groups in the prevalence of EPDS ≥11, EPDS scores over time, or in changes in EPDS scores from pregnancy to postpartum in either the ITT or per-protocol analyses. Women in the fish oil group with previous history of depression presented a higher reduction on the EPDS score from the second to the third trimester in the fish oil comparing to the control group in the ITT analyses [−1.0 (−3.0–0.0) vs. -0.0 (−1.0–3.0), P = 0.038). These results were confirmed on the LME model (β = −3.441; 95%CI: -6.532– -0.350, P = 0.029). Conclusion: Daily supplementation of 1.8 g of n-3 PUFAs during 16 weeks did not prevent maternal depressive symptoms in a sample of Brazilian women

Fine-Tuning Roles of Endogenous Brain-Derived Neurotrophic Factor, TrkB and Sortilin in Colorectal Cancer Cell Survival

International audienceBACKGROUND: Neurotrophin receptors were initially identified in neural cells. They were recently detected in some cancers in association with invasiveness, but the function of these tyrosine kinase receptors was not previously investigated in colorectal cancer (CRC) cells. METHODS AND FINDINGS: We report herein that human CRC cell lines synthesize the neural growth factor Brain-derived neurotrophic factor (BDNF) under stress conditions (serum starvation). In parallel, CRC cells expressed high- (TrkB) and low-affinity (p75(NTR)) receptors at the plasma membrane, whereas TrkA and TrkC, two other high affinity receptors for NGF and NT-3, respectively, were undetectable. We demonstrate that BDNF induced cell proliferation and had an anti-apoptotic effect mediated through TrkB, as assessed by K252a, a Trk pharmacologic inhibitor. It suppressed both cell proliferation and survival of CRC cells that do not express TrkA nor TrkC. In parallel to the increase of BDNF secretion, sortilin, a protein acting as a neurotrophin transporter as well as a co-receptor for p75(NTR), was increased in the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin could regulate neurotrophin transport in these cells. However, pro-BDNF, also detected in CRC cells, was co-expressed with p75(NTR) at the cell membrane and co-localized with sortilin. In contrast to BDNF, exogenous pro-BDNF induced CRC apoptosis, which suggests that a counterbalance mechanism is involved in the control of CRC cell survival, through sortilin as the co-receptor for p75(NTR), the high affinity receptor for pro-neurotrophins. Likewise, we show that BDNF and TrkB transcripts (and not p75(NTR)) are overexpressed in the patients' tumors by comparison with their adjacent normal tissues, notably in advanced stages of CRC. CONCLUSION: Taken together, these results highlight that BDNF and TrkB are essential for CRC cell growth and survival in vitro and in tumors. This autocrine loop could be of major importance to define new targeted therapies