Research paperDietary n-3 PUFA, fish consumption and depression: A systematic review and meta-analysis of observational studies
Introduction
Over the last four decades, polyunsaturated fatty acids (PUFA) have been studied in relation to prevention of cardiovascular diseases (CVD) (Sanchez-Villegas and Martinez-Gonzalez, 2013). The highest representative compounds consumed by humans belong to the n-3 and n-6 family of PUFA, including alpha-linolenic acid (ALA) and linoleic acid (LA), respectively (Grosso et al., 2014a). Once consumed in the diet, LA undergoes to transformation in arachidonic acid (AA), which is precursor of pro-inflammatory cytokines, whereas ALA is converted into eicosapentaenoic acid (EPA), with a subsequent elongation to docosahexaenoic acid (DHA). EPA and DHA may also be consumed directly through ingestion of fish and seafood. The beneficial effect of n-3 PUFA is supposed to depend on their capacity to positively modulate the immune and inflammatory response (Gil, 2002, Tapiero et al., 2002), as they demonstrated a certain efficacy in preventing illnesses with an inflammatory component (Parletta et al., 2013). An emerging body of data indicates n-3 PUFA as potential candidates in the prevention and treatment of psychiatric diseases involving inflammatory processes, such as depressive disorders (Bourre, 2007). Ecological studies showed that dietary intakes of fish correlate with lower prevalence of major depression (Hibbeln, 1998), bipolar disorder (Noaghiul and Hibbeln, 2003), and post-partum depression (Hibbeln, 2002). These findings suggested that cross-national variations in n-3 PUFA intake contained in fish are inversely correlated with the prevalence of depression.
The potential benefits of n-3 PUFA intake in preventing or treating psychiatric illnesses, such as depressive disorders, are biologically plausible. Major depression shares certain pathophysiological mechanisms with CVD, such as increased production of pro-inflammatory cytokines, endothelial dysfunction, and elevations in plasma homocysteine levels (Hepgul et al., 2010). Several studies have shown a positive correlation between the severity of the symptoms of depression and the increase in the inflammatory status (Maes et al., 2009). Major depression has been recently considered secondary to a systemic inflammatory disorder in which pro-inflammatory cytokines alter serotonin metabolism, reduce synaptic plasticity, and increase the risk of developing diseases associated with an inflammatory state (Caraci et al., 2010, Huffman et al., 2013, Maes et al., 2009). According to this scenario, the anti-inflammatory capacity of n-3 PUFA has been hypothesized to play a central role in counteracting inflammatory processes occurring in depression (Parletta et al., 2013). Another possible mechanism may depend on n-3 PUFA neuro-endocrine metabolism, release, uptake, and receptor action (Hibbeln et al., 1998). N-3 PUFA have been shown to interact with serotonin metabolism by facilitating its release by inhibiting the formation of E2-series prostaglandins and increasing membrane fluidity (Patrick and Ames, 2015). Their positive effects on depression may also depend on their physiological abundant content in the human nervous system and their involvement in neurogenesis and neuroplasticity (Bourre, 2004).
There is evidence that depressed patients have decreased content of n-3 PUFA in plasma and erythrocyte membrane, supporting the mechanistic links between n-3 PUFA deficiency and increased risk of depression (De Vriese et al., 2003, Edwards et al., 1998, Peet et al., 1998). A number of cross-sectional and prospective investigations have been performed to test the potential association between fish consumption, n-3 PUFA dietary intake and depression, but findings are contrasting (Giles et al., 2013). The use of n-3 PUFA supplements as add-on therapy for major depression (in addition to first and second generation antidepressant drugs) appears promising but observational studies analyzing free-living populations did not yield to strong conclusions on the potential protective role of n-3 PUFA in preventing depressive disorders (Grosso et al., 2014b). Indeed, it is still unclear whether a biological response to dietary n-3 PUFA can be obtained in a dose-dependent manner with clinically relevant effects in the general population. Thus, the main aim of this study was to systematically review observational studies exploring the association between fish, n-3 PUFA dietary consumption and depression. A meta-analysis of risk estimates to calculate effect-size and eventually define the dose-response effect was performed.
Section snippets
Search strategy and selection of the studies
A comprehensive search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of Systematic Reviews of all observational studies evaluating the effects of n-3 PUFA on depression in cohort of individuals published up to August 2014 was performed. Articles of potential interest were identified using the following search terms: “omega-3”, “polyunsaturated fatty acids”, “PUFA”, “EPA”, “DHA”, “alpha linolenic acid”, “linoleic acid”, combined with the following terms: “depression”, “depressive
Study characteristics
The process of identification and inclusion of studies is summarized in Fig. 1. Among the 232 articles retrieved, observational studies were identified and screened by reading the abstract and, when necessary, the full text. Twenty-six out of the 57 articles considered potentially relevant were excluded and not assessed further for the following reasons: 2 reported insufficient statistics or did not present crucial data, 7 were conducted on n-3 PUFA in tissues, 7 had different study design, 10
Discussion
Results of this systematic review and meta-analysis supported the hypothesis that fish consumption and n-3 PUFA intake are associated with decreased risk of depression. To date, this is the first meta-analysis pooling together all relevant observational studies assessing the relation between fish, n-3 PUFA intake and depression, providing insights on dose-response relationship. A significant decreased risk was found for 50 g/d intake of fish, 1.8 g/d intake of n-3 PUFA, and 0.6 g/d intake of
Contributors
GG designed the research; GG and SC conducted research; GG and AM analyzed data; SM edited tables and images; GG wrote the paper; GG, FG, and AM provided important revision for final content. All authors reviewed and approved the study content.
Role of the funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
All authors declare no conflicts of interest.
Acknowledgments
None.
References (73)
- et al.
Depressed mood and dietary fish intake: direct relationship or indirect relationship as a result of diet and lifestyle?
J. Affect. Disord.
(2007) - et al.
Association of fish and long-chain n-3 polyunsaturated fatty acid intakes with the occurrence of depressive episodes in middle-aged French men and women
Prostaglandins Leukot. Essent. Fat. Acids
(2008) - et al.
Omega-3 fatty acid intakes are inversely related to elevated depressive symptoms among United States women
J. Nutr.
(2013) Dietary omega-3 fatty acids for women
Biomed. Pharm.
(2007)- et al.
Depression and Alzheimer's disease: neurobiological links and common pharmacological targets
Eur. J. Pharmacol.
(2010) - et al.
Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women
Nutrition
(2009) - et al.
Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression
Life Sci.
(2003) - et al.
Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients
J. Affect. Disord.
(1998) Polyunsaturated fatty acids and inflammatory diseases
Biomed. Pharm.
(2002)Fish consumption and major depression
Lancet
(1998)