Eicosanoids are arachidonic acid (AA) derivatives belonging to a family of lipid signalling
mediators that are engaged in both physiological and pathological processes in the brain.
Recently, their implication in the prolonged inflammatory response has become a focus of particular
interest because, in contrast to acute inflammation, chronic inflammatory processes within the
central nervous system (CNS) are crucial for the development of brain pathologies including depression.
The synthesis of eicosanoids is catalysed primarily by cyclooxygenases (COX), which are involved
in the production of pro-inflammatory AA metabolites, including prostaglandins and thromboxanes.
Moreover, eicosanoid synthesis is catalysed by lipoxygenases (LOXs), which generate both
leukotrienes and anti-inflammatory derivatives such as lipoxins. Thus, AA metabolites have double-
edged pro-inflammatory and anti-inflammatory, pro-resolving properties, and an imbalance between
these metabolites has been proposed as a contributor or even the basis for chronic neuroinflammatory
This review focuses on important evidence regarding eicosanoid-related pathways (with special emphasis
on prostaglandins and lipoxins) that has added a new layer of complexity to the idea of targeting
the double-edged AA-derivative pathways for therapeutic benefits in depression. We also
sought to explore future research directions that can support a pro-resolving response to control the
balance between eicosanoids and thus to reduce the chronic neuroinflammation that underlies at
least a portion of depressive disorders.