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      Membrane Omega-3 Fatty Acid Deficiency as a Preventable Risk Factor for Comorbid Coronary Heart Disease in Major Depressive Disorder

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      Cardiovascular Psychiatry and Neurology
      Hindawi Publishing Corporation

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          Abstract

          Major depression disorder (MDD) significantly increases the risk for coronary heart disease (CHD) which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS) and increases risk for mortality. Here evidence implicating omega-3 (n-3) fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

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          Most cited references158

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          Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.

          Despite nearly 40 years of research, the role of plasma triglyceride as a risk factor for cardiovascular disease remains elusive. The objectives of the present study were to quantify the magnitude of the association between triglyceride and cardiovascular disease in the general population, and to determine whether this relationship is independent of high-density lipoprotein (HDL) cholesterol, using the semi-quantitative techniques of metaanalysis. Seventeen studies were selected for the analysis based on published reports of population-based, prospective studies, including 46413 men and 10864 women. To insure comparability, only studies reporting the association between fasting triglyceride levels and incident cardiovascular endpoints were included. Using standard meta-analysis calculations, relative risks (RR) and 95% confidence intervals (CI) were calculated and standardized with respect to a 1 mmol/l increase in triglyceride. Multivariable-adjusted RRs were determined for the six studies in men and two studies in women that reported adjustments for HDL cholesterol. For men and women, the univariate RRs for triglyceride were 1.32 (95% Cl 1.26-1.39) and 1.76 (95% Cl 1.50-2.07), respectively, indicating an approximately 30% increased risk in men and a 75% increase in women. Adjustment of HDL cholesterol and other risk factors attenuated these RRs to 1.14 (95% Cl 1.05-1.28) and 1.37 (95% Cl 1.13-1.66), respectively, which were still statistically significant values. Based on combined data from prospective studies, triglyceride is a risk factor for cardiovascular disease for both men and women in the general population, independent of HDL cholesterol. These finding demonstrate the necessity for clinical trials to evaluate whether lowering plasma triglyceride decreases the risk of cardiovascular disease.
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            Genetic epidemiology of major depression: review and meta-analysis.

            The authors conducted a meta-analysis of relevant data from primary studies of the genetic epidemiology of major depression. The authors searched MEDLINE and the reference lists of previous review articles to identify relevant primary studies. On the basis of a review of family, adoption, and twin studies that met specific inclusion criteria, the authors derived quantitative summary statistics. Five family studies met the inclusion criteria. The odds ratios for proband (subjects with major depression or comparison subjects) versus first-degree relative status (affected or unaffected with major depression) were homogeneous across the five studies (Mantel-Haenszel odds ratio=2.84, 95% CI=2.31-3.49). No adoption study met the inclusion criteria, but the results of two of the three reports were consistent with genetic influences on liability to major depression. Five twin studies met the inclusion criteria, and their statistical summation suggested that familial aggregation was due to additive genetic effects (point estimate of heritability of liability=37%, 95% CI=31%-42%), with a minimal contribution of environmental effects common to siblings (point estimate=0%, 95% CI=0%-5%), and substantial individual-specific environmental effects/measurement error (point estimate=63%, 95% CI=58%-67%). The literature suggests that recurrence best predicts the familial aggregation of major depression. Major depression is a familial disorder, and its familiality mostly or entirely results from genetic influences. Environmental influences specific to an individual are also etiologically significant. Major depression is a complex disorder that does not result from either genetic or environmental influences alone but rather from both. These findings are notably consistent across samples and methods and are likely to be generally applicable.
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              Genetic susceptibility to death from coronary heart disease in a study of twins.

              A family history of premature coronary heart disease has long been thought to be a risk factor for coronary heart disease. Using data from 26 years of follow-up of 21,004 Swedish twins born between 1886 and 1925, we investigated this issue further by assessing the risk of death from coronary heart disease in pairs of monozygotic and dizygotic twins. The study population consisted of 3298 monozygotic and 5964 dizygotic male twins and 4012 monozygotic and 7730 dizygotic female twins. The age at which one twin died of coronary heart disease was used as the primary independent variable to predict the risk of death from coronary heart disease in the other twin. Information about other risk factors was obtained from questionnaires administered in 1961 and 1963. Actuarial life-table analysis was used to estimate the cumulative probability of death from coronary heart disease. Relative-hazard estimates were obtained from a multivariate survival analysis. Among the men, the relative hazard of death from coronary heart disease when one's twin died of coronary heart disease before the age of 55 years, as compared with the hazard when one's twin did not die before 55, was 8.1 (95 percent confidence interval, 2.7 to 24.5) for monozygotic twins and 3.8 (1.4 to 10.5) for dizygotic twins. Among the women, when one's twin died of coronary heart disease before the age of 65 years, the relative hazard was 15.0 (95 percent confidence interval, 7.1 to 31.9) for monozygotic twins and 2.6 (1.0 to 7.1) for dizygotic twins. Among both the men and the women, whether monozygotic or dizygotic twins, the magnitude of the relative hazard decreased as the age at which one's twin died of coronary heart disease increased. The ratio of the relative-hazard estimate for the monozygotic twins to the estimate for the dizygotic twins approached 1 with increasing age. These relative hazards were little influenced by other risk factors for coronary heart disease. Our findings suggest that at younger ages, death from coronary heart disease is influenced by genetic factors in both women and men. The results also imply that the genetic effect decreases at older ages.
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                Author and article information

                Journal
                Cardiovasc Psychiatry Neurol
                CPN
                Cardiovascular Psychiatry and Neurology
                Hindawi Publishing Corporation
                2090-0163
                2090-0171
                2009
                16 September 2009
                : 2009
                : 362795
                Affiliations
                Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
                Author notes
                *Robert K. McNamara: robert.mcnamara@ 123456uc.edu

                Recommended by Radmila M. Manev

                Article
                10.1155/2009/362795
                2774576
                19936106
                4ee91513-ebe7-446f-ace6-d23ccefce9da
                Copyright © 2009 Robert K. McNamara.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 May 2009
                : 10 July 2009
                Categories
                Review Article

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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