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. 2016 Sep;5:96-106.
doi: 10.1016/j.jnim.2016.04.004. Epub 2016 May 4.

Role of Omega-3 Fatty Acids in the Etiology, Treatment, and Prevention of Depression: Current Status and Future Directions

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Free PMC article

Role of Omega-3 Fatty Acids in the Etiology, Treatment, and Prevention of Depression: Current Status and Future Directions

Robert K McNamara. J Nutr Intermed Metab. .
Free PMC article

Abstract

Over the past three decades a body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of major depressive disorder (MDD). Cross-national and cross-sectional data suggest that greater habitual intake of preformed EPA+DHA is associated with reduced risk for developing depressive symptoms and syndromal MDD. Erythrocyte EPA and DHA composition is highly correlated with habitual fish or fish oil intake, and case-control studies have consistently observed lower erythrocyte EPA and/or DHA levels in patients with MDD. Low erythrocyte EPA+DHA composition may also be associated with increased risk for suicide and cardiovascular disease, two primary causes of excess premature mortality in MDD. While controversial, dietary EPA+DHA supplementation may have antidepressant properties and may augment the therapeutic efficacy of antidepressant medications. Neuroimaging and rodent neurodevelopmental studies further suggest that low LCn-3 fatty acid intake or biostatus can recapitulate central pathophysiological features associated with MDD. Prospective findings suggest that low LCn-3 fatty acid biostatus increases risk for depressive symptoms in part by augmenting pro-inflammatory responsivity. When taken collectively, these translational findings provide a strong empirical foundation in support of dietary LCn-3 fatty acid deficiency as a modifiable risk factor for MDD. This review provides an overview of this translational evidence and then discusses future directions including strategies to translate this evidence into routine clinical screening and treatment algorithms.

Keywords: Docosahexaenoic acid (DHA); Eicosapentaenoic acid (EPA); Long-chain omega-3 fatty acids; Major depressive disorder.

Figures

Figure 1
Figure 1
Diagram illustrating the biosynthetic pathway of omega-3 fatty acids. The biosynthesis of docosahexaenoic acid (DHA, 22:6n-3) from dietary α-linolenic acid (18:3n-3) requires a series of microsomal elongation (ELOVL5) and delta-5 (FADS1) and delta-6 desaturase (FADS2) mediated reactions. The final synthesis of DHA is catalyzed by β-oxidation within peroxisomes. Metabolism of DHA yields inflammation-resolving docosanoids. Preformed DHA and EPA can also be obtained directly from the diet.
Figure 2
Figure 2
Comparison of the mean erythrocyte ‘omega-3 index’ (EPA+DHA composition) in adult patients with acute coronary syndrome (ACS) residing in the U.S. (n=768)(Block et al., 2008), adult patients with MDD residing in the Chicago area (n=20)(McNamara et al., 2010a), normative values from a cohort of subjects residing in the U.S. (n=11,329, http://www.omegaquant.com/fatty-acids-regularly-measured/), and adults residing in Japan (n=456)(Itomura et al., 2008). Proposed ‘risk zones’ for sudden cardiac death derived from prospective longitudinal studies are indicated (Harris & Von Schacky, 2004). Note that MDD patients exhibit an ‘omega-3 index’ that is similar to patients with ACS, and places them at ‘high risk’ for sudden cardiac arrest. In view of evidence implicating both EPA and DHA deficiency in the pathophysiology of MDD, it is proposed that similar ‘risk zones’ be adopted in psychiatric practice to identify patients requiring corrective supplementation. Controlled intervention studies suggest that daily EPA+DHA doses of 1-2 g are sufficient to increase erythrocyte EPA+DHA composition to levels ≥4% (Flock et al., 2013).

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