Publications

OBJECTIVE

Experimental and observational data suggest that a higher dietary intake of long-chain omega-3 polyunsaturated acids may lead to a decreased risk of depressive disorders. We assessed multivariable-adjusted associations of fish consumption and dietary intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with depressive symptoms in a population-based sample of 3317 African-American and Caucasian men and women from the Coronary Artery Risk Development in Young Adults study.

METHODS

Diet was assessed in year 7 (1992-1993) and depressive symptoms were measured in years 10 (1995-1996), 15 (2000-2001), and 20 (2005-2006) by the 20-item Center for Epidemiological Studies Depression Scale. Depressive symptoms were defined as a Center for Epidemiological Studies Depression Scale score > or =16 or self-reported use of antidepressant medication.

RESULTS

In the entire cohort, the highest quintiles of intakes of EPA (> or =0.03% energy), DHA (> or =0.05% energy), and EPA + DHA (> or =0.08% energy) were associated with a lower risk of depressive symptoms at year 10 (P for trends = 0.16, 0.10, and 0.03, respectively). The observed inverse associations were more pronounced in women. For the total number of occasions with depressive symptoms, the multivariable adjusted odds ratios (95% confidence interval) in women were 0.75 (0.55-1.01) for fish intake, 0.66 (0.50-0.89) for EPA, 0.66 (0.49-0.89) for DHA, and 0.71 (0.52-0.95) for EPA + DHA when comparing the highest with the lowest quintiles. Analyses of continuous Center for Epidemiological Studies Depression Scale scores revealed inverse associations with fourth-root-transformed omega-3 variables in women.

CONCLUSION

Our findings suggest that dietary intakes of fish and long-chain omega-3 fatty acids may be inversely associated with chronic depressive symptoms in women.

Guanine nucleotide exchange factors (GEFs) stimulate guanine nucleotide exchange and the subsequent activation of Rho-family proteins in response to extracellular stimuli acting upon cytokine, tyrosine kinase, adhesion, integrin, and G-protein-coupled receptors (GPCRs). Upon Rho activation, several downstream events occur, such as morphological and cytoskeletal changes, motility, growth, survival, and gene transcription. The leukemia-associated RhoGEF (LARG) is a member of the regulators of G-protein signaling homology domain (RH) family of GEFs originally identified as a result of chromosomal translocation in acute myeloid leukemia. Using a novel fluorescence polarization guanine nucleotide-binding assay using BODIPY-Texas Red-GTPgammaS (BODIPY-TR-GTPgammaS), the authors performed a 10,000-compound high-throughput screen for inhibitors of LARG-stimulated RhoA nucleotide binding. Five compounds identified from the high-throughput screen were confirmed in a nonfluorescent radioactive guanine nucleotide-binding assay measuring LARG-stimulated [( 35)S] GTPgammaS binding to RhoA, thus ruling out nonspecific fluorescent effects. All 5 compounds selectively inhibited LARG-stimulated RhoA [( 35)S] GTPgammaS binding but had little to no effect on RhoA or Galpha( o) [(35)S] GTPgammaS binding. Therefore, these 5 compounds should serve as promising starting points for the development of small-molecule inhibitors of LARG-mediated nucleotide exchange as both pharmacological tools and therapeutics. In addition, the fluorescence polarization guanine nucleotide-binding assay described here should serve as a useful approach for both high-throughput screening and general biological applications.

The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.