The overlap between cardiovascular disease and depression has also been noted, with omega-3 status emerging as a common thread. Indeed, major depression in acute coronary syndrome patients is associated with significantly lower plasma levels of omega-3 fatty acids, particularly DHA [29]. In addition, elevated homocysteine levels, a known risk factor for cardiovascular disease, has been associated with the excess omega-6 fatty acids found in the Western diet [30]. Finally, lowered intake of the parent omega-3 ALA has been associated with depression in 771 Japanese patients with newly diagnosed lung cancer [31].

It is important to note that not every study supports an association between lowered omega-3 status and depression. Two studies have actually shown significant increases in plasma and RBC omega-3 status among depressed patients [32,33]. A recent study involving depressed adolescent patients found no significant relationship between adipose tissue EFA levels and depression [34].

Possible mechanisms of omega-3 EFA

Detailed reviews of the possible neurobehavioral mechanisms of omega-3 fatty acids have been previously published and are beyond the scope of this review [35,36]. The influence of omega-3 fatty acids within the CNS is far from completely understood, and our current knowledge is largely based on the consequences of omega-3 deficiency within animal models. There are two major areas of omega-3 fatty acid influence worthy of further discussion. The first is the importance of omega-3 fatty acids in neuronal membranes. Omega-3 fatty acids are an essential component of CNS membrane phospholipid acyl chains and are therefore critical to the dynamic structure and function of neuronal membranes [37]. Proteins are embedded in the lipid bi-layer of the cell and the conformation or quaternary structure of these proteins is sensitive to the lipid components. The proteins in the bi-layer have critical cellular functions as they act as transporters and receptors. Omega-3 fatty acids can alter membrane fluidity by displacing cholesterol from the membrane [38]. An optimal fluidity, influenced by EFAs, is required for neurotransmitter binding and the signaling within the cell [39]. EFAs can act as sources for second messengers within and between neurons [35].

The second area where omega-3 fatty acids may exert significant influence in major depression is via cytokine modulation. A growing body of research has documented an association between depression and the production these proinflammatory immune chemicals. These cytokines, including interleukin-1 beta (IL-1β), -2 and -6, interferon-gamma, and tumor necrosis factor alpha (TNFα), can have direct and indirect effects on the CNS. Some of the documented activities of these cytokines include lowered neurotransmitter precursor availability, activation of the hypothalamic-pituitary axis, and alterations of the metabolism of neurotransmitters and neurotransmitter mRNA [40]. Researchers have found elevations of IL-1β, and TNFα are associated with the severity of depression [41]. Psychological stress can cause an elevation of these cytokines. It is worth noting that various tricyclic and selective serotonin re-uptake inhibiting antidepressants can inhibit the release of these inflammatory cytokines [40].

Omega-3 fatty acids, and EPA in particular, are well documented inhibitors of proinflammatory cytokines such as IL-1 β and TNFα. In addition, it has recently been suggested that the anti-inflammatory role of omega-3 fatty acids may influence brain derived neurotrophic factor (BDNF) in depression [36]. BDNF is a polypeptide that supports the survival and growth of neurons through development and adulthood. Serum BDNF has been found to be negatively correlated with the severity of depressive symptoms [42]. Antidepressant medications and voluntary exercise can enhance BDNF, while diets high in saturated fat and sucrose, and psychological stress inhibit BDNF production [36].