Abstract: A growing body of evidence suggests that n-3 polyunsaturated fatty acid (n-3PUFA) is associated with depressive disorder, and supplementation of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are the most common PUFA in the brain, may be of value in the prevention and treatment of depression. The purpose of this article is to review studies in this emerging area, identify and evaluate available evidence of a negative correction between n-3PUFA intake and depression, and propose mechanisms that could explain such relationship. n-3PUFA may play an etiological role in serotonergic transmission, glucose metabolism, and release of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF) level, and neuronal apoptosis. Future studies are needed to examine the dosage response functions of n-3PUFA, the specific roles of DHA or EPA in different clusters of depressive symptoms, whether DHA or EPA is effective in antidepressant treatments independently or coefficiently, as well as the potential clinical value of n-3PUFA in major depression.

Key words: n-3PUFA, DHA, EPA, depression, neural mechanism, 5-HT, BDNF