Omega-3 and Omega-6 Polyunsaturated Fatty Acids in Bipolar Disorder: A Review of Biomarker and Treatment Studies.

Objective: There is growing evidence that 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 data on PUFAs as biomarkers in bipolar disorder and n-3 PUFA used as treatment for bipolar disorder.

Data Sources: PubMed and CINAHL were searched for articles on PUFA and bipolar disorder published in the English language through November 6, 2013, with an updated search conducted on August 20, 2015. Keywords searched included omega 3 fatty acids and bipolar disorder, omega 3 fatty acids and bipolar mania, omega 3 fatty acids and bipolar depression, omega 3 fatty acids and mania, omega 3 fatty acids and cyclothymia, omega 3 fatty acids and hypomania, fatty acids and bipolar disorder, essential fatty acids and bipolar disorder, polyunsaturated fatty acids and bipolar disorder, DHA and bipolar disorder, and EPA and bipolar disorder.

Study Selection: Studies selected measured PUFAs as biomarkers or introduced n-3 PUFA as treatment.

Results: We identified 17 relevant human clinical articles that either compared PUFA levels between a bipolar disorder group and a control group or used a PUFA intervention to treat depression or mania in bipolar disorder. Human studies suggest low n-3 red blood cell PUFA concentrations and correlations with clinical severity in studies of plasma concentrations in symptomatic bipolar disorder. Results of published n-3 PUFA dietary supplementation trials for bipolar disorder indicate efficacy in treatment for mania or depression in 5 of 5 open-label trials, efficacy in treatment of depression in 1 of 7 randomized controlled trials, and a signal for treatment of depression in 1 meta-analysis.

Conclusions: 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.