Reconsidering Dietary Polyunsaturated Fatty Acids in Bipolar Disorder: A Translational Picture

Inflammation is an important mediator of pathophysiology in bipolar disorder. The omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) metabolic pathways participate in several inflammatory processes and have been linked through epidemiologic and clinical studies to bipolar disorder and its response to treatment. We review the proposed role of PUFA metabolism in neuroinflammation, modulation of brain PUFA metabolism by antimanic medications in rodent models, and anti-inflammatory pharmacotherapy in bipolar disorder and in major depressive disorder (MDD). Although the convergence of findings between preclinical and postmortem clinical data is compelling, we investigate why human trials of PUFA as treatment are mixed. We view the biomarker and treatment study findings in light of the evidence for the hypothesis that arachidonic acid hypermetabolism contributes to bipolar disorder pathophysiology and propose that a combined high n-3 plus low n-6 diet should be tested as an adjunct to current medication in future trials.