Dr Geoffrey Schrader
University of Adelaide
$222,594 from beyondblue – Total funding $445,188
Cardiovascular Disease and Depression Strategic Research Program
Project completion year
Depression is a significant co-morbid condition which impacts adversely on the prognosis and management of cardiac disease.1 Local studies 2-4 confirm that depression is highly prevalent in people with cardiac disease and is associated with adverse outcomes. However, the nature of that association remains unclear. Although depression in cardiac patients can be successfully treated 5,6, there is no evidence as yet that treating depression leads to improved cardiac outcomes.
The long-chain omega-3 (LC n-3) polyunsaturated fatty acids (PUFA) in fish oil, viz. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have the potential to improve both cardiac conditions and depression and as such offer a unique therapeutic approach to optimise outcomes for individuals suffering these co-morbidities.
The importance of LC n-3 intake for cardiovascular health is now well recognised by health authorities in Australia and internationally. This has led to the introduction of Nutrient Reference Values for LC n-3 intake by the National Health and Medical Research Council in Australia and the approval of a health claim for LC n-3 intake by the Food and Drug Administration in the USA. From 2008 a pre-approved general level health claim for LC n-3 will be introduced into legislation following approval by Food Standards Australia and New Zealand. The American Heart Association7 recommends daily consumption of 1g EPA + DHA/day in established cardiac disease. However, the extent to which any long-term benefit of LC n-3 intake in cardiac patients may be influenced by impacts on mood is yet to be evaluated.
There is growing evidence for a role of LC n-3 supplementation in the treatment of mood disorders, although the optimal type and dose is yet to be established and will depend on the nature of the condition.8-11 As DHA is a primary component of brain tissue, it is often assumed that consumption of fish or fish oil aids mental health by augmenting DHA-dependent neurotransmitter mechanisms. Surprisingly, however, most studies demonstrating improvement of mental health have administered EPA-rich fish oil, even though there is very little EPA in the brain, and studies such as that conducted by CI Howe12 in major depression have failed to show benefit with DHA supplementation. Thus any antidepressant effect of fish oil seems unlikely to be mediated by DHA in neural tissue.
The aim of this project is to evaluate, in a randomised controlled trial, the potential for LC n-3 supplementation to relieve depressive symptoms and improve health status in cardiac patients suffering from depression. The researchers will explore potential mechanisms mediating these benefits with particular reference to the abovementioned hypotheses, viz. that their depression may be due to peripheral as well as central pathogenic abnormalities, including impairments of endothelial function in cerebral vessels and abnormalities of serotonin transport.
Findings may lead to development of evidence-based, simple therapeutic recommendations (#3) which can be broadly applied in a number of Australian health care settings.
In patients with angiographically-documented coronary artery disease and co-morbid depression, dietary supplementation with EPA-rich fish oil over six months will influence the severity of depressive symptoms.
In patients with angiographically-documented coronary artery disease and co-morbid depression, dietary supplementation with EPA-rich fish oil over 6 months will lead to significant changes in quality of life measures, as assessed by the SF-36 physical and mental summary scores.
In patients with angiographically-documented coronary artery disease and co-morbid depression, dietary supplementation with EPA-rich fish oil over six months will lead to significant reduction in angina frequency as assessed by the Seattle Angina Questionnaire.
Erythrocyte levels of n-3 PUFA, in particular EPA, will be related to the magnitude of improvement in depressive symptoms, quality of life and angina scores.
Changes in depression severity will be correlated with changes in endothelial vasodilator function assessed by brachial artery FMD and cerebral blood flow assessed using TCD.
The presence of the serotonin transporter gene S-allele will be associated with differences in depression severity, SF-36 quality of life scores and Seattle Angina Questionnaire scores.
1 Bunker SJ, Colquhoun DM, Esler MD et al. ”Stress” and coronary heart disease: psychosocial risk factors. Med J Aust 2003;178(6):272-6.
2 Wade V, Cheok F, Schrader G, Hordacre A, Marker J. Depression after cardiac hospitalization; The Identifying Depression as a Comorbid Condition (IDACC) study. Aust Fam Physician 2005;34:985-9.
3 Schrader GD, Cheok F, Hordacre AL, Marker J. Predictors of depression 12 months after cardiac hospitalization: the IDACC study. Aust NZ Psychiatry 2006;40:1025-1030.
4 Schrader GD, Cheok F, Hordacre A, Guiver N. Predictors of depression three months after cardiac hospitalization. Psychosom Med 2004;66:514-20.
5 Schrader GD, Cheok F, Hordacre AL, Marker J, Wade V. Effect of psychiatry liaison with general practitioners on depression severity in recently hospitalized cardiac patients: a randomised controlled trial. Med J Aust 2005;182:272-6.
6 Cheok F, Schrader G, Banham D, Marker J, Hordacre A. Identification and treatment of depression following admission for a cardiac condition: rationale and baseline findings of the IDACC project. Am Heart J 2003;146:978-84.
7 Lichtenstein AH, Appel LJ, Brands M et al. Summary of American Heart Association diet and lifestyle recommendations revision 2006. Arterioscler Thromb Vasc Biol 2006;26(10):2186-91.
8 Hibbeln JR, Salem N Jr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr 1995;62:1-9.
9 Peet M, Stokes C. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs 2005;65(8):1051-9.
10 Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev 2005;45:1-28.
11 Sinclair AJ, Begg D, Mathai M, Weisinger RS. Omega 3 fatty acids and the brain: review of studies in depression. Asia Pac J Clin Nutr 2007;16(Suppl 1):391-397.
12 Grenyer BFS, Crowe T, Meyer B, Owen AJ, Grigonis-Deane EM, Caputi P, Howe PRC. Fish oil supplementation in the treatment of major depression: A randomised double-blind placebo-controlled trial. Prog Neuro-Psychopharmacol Biol Psychiatry 2007;31:1393-6.