title: Omega-3 and Omega-6 Polyunsaturated Fatty Acids in Bipolar Disorder: A Review of Biomarker and Treatment Studies.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, 500 University Dr, PO Box 850, Mail Code: HO73, Hershey, PA 17033-0850. esaunders@hmc.psu.edu.|Department of Psychiatry, Penn State College of Medicine and Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.|Department of Psychiatry and Depression Center, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Erika F H
authors.initials: EF
authors.lastname: Saunders
authors.affiliation: Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Ramsden
authors.affiliation: Department of Psychiatry, Penn State College of Medicine and Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.
authors.forename: Mostafa S
authors.initials: MS
authors.lastname: Sherazy
authors.affiliation: Department of Psychiatry, Penn State College of Medicine and Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Gelenberg
authors.affiliation: Department of Psychiatry, University of Illinois, Chicago, Illinois, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Davis
authors.affiliation: Office of Scientific Director, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001714:Bipolar Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015525:Fatty Acids, Omega-3 / Q000097:blood* / Q000627:therapeutic use*; D043371:Fatty Acids, Omega-6 / Q000097:blood* / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6