Biomarker studies of PUFA and treatment studies of n-3 PUFA in bipolar disorder show promise for indicating a way forward in the study of PUFA in bipolar disorder. Investigation of the intake and metabolism of the n-3 and n-6 PUFA when supplementation is provided in treatment trials might offer clues for identification of when and how PUFA may be important for treatment in bipolar disorder.
Inflammation is an important mediator of pathophysiology in bipolar disorder (BD). The omega (n)-3 and omega (n)-6 polyunsaturated fatty acid (PUFA) metabolic pathways participate in several inflammatory processes, and have been linked through epidemiological and clinical studies to BD 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 BD and in major depressive disorder (MDD). Though the convergence of findings between pre-clinical and post-mortem 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 (AA) hypermetabolism contributes to BD 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.
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