title: Dietary intake and plasma metabolomic analysis of polyunsaturated fatty acids in bipolar subjects reveal dysregulation of linoleic acid metabolism.
abstract: Polyunsaturated fatty acids (PUFA) profiles associate with risk for mood disorders. This poses the hypothesis of metabolic differences between patients and unaffected healthy controls that relate to the primary illness or are secondary to medication use or dietary intake. However, dietary manipulation or supplementation studies show equivocal results improving mental health outcomes. This study investigates dietary patterns and metabolic profiles relevant to PUFA metabolism, in bipolar I individuals compared to non-psychiatric controls. We collected seven-day diet records and performed metabolomic analysis of fasted plasma collected immediately after diet recording. Regression analyses adjusted for age, gender and energy intake found that bipolar individuals had significantly lower intake of selenium and PUFAs, including eicosapentaenoic acid (EPA) (n-3), docosahexaenoic acid (DHA) (n-3), arachidonic acid (AA) (n-6) and docosapentaenoic acid (DPA) (n-3/n-6 mix); and significantly increased intake of the saturated fats, eicosanoic and docosanoic acid. Regression analysis of metabolomic data derived from plasma samples, correcting for age, gender, BMI, psychiatric medication use and dietary PUFA intake, revealed that bipolar individuals had reduced 13S-HpODE, a major peroxidation product of the n-6, linoleic acid (LA), reduced eicosadienoic acid (EDA), an elongation product of LA; reduced prostaglandins G2, F2 alpha and E1, synthesized from n-6 PUFA; and reduced EPA. These observations remained significant or near significant after Bonferroni correction and are consistent with metabolic variances between bipolar and control individuals with regard to PUFA metabolism. These findings suggest that specific dietary interventions aimed towards correcting these metabolic disparities may impact health outcomes for individuals with bipolar disorder.
authors: Department of Psychiatry, University of Michigan, United States. Electronic address: evanssi@umich.edu.
authors: Simon J
authors: SJ
authors: Evans
authors: Department of Psychiatry, University of Michigan, United States.
authors: Rachel N
authors: RN
authors: Ringrose
authors: Department of Psychiatry, University of Michigan, United States.
authors: Gloria J
authors: GJ
authors: Harrington
authors: Department of Environment Health Sciences, University of Michigan, United States.
authors: Peter
authors: P
authors: Mancuso
authors: Department of Internal Medicine, University of Michigan, United States.
authors: Charles F
authors: CF
authors: Burant
authors: Department of Psychiatry, University of Michigan, United States.
authors: Melvin G
authors: MG
authors: McInnis
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000378:metabolism*; D004034:Diet Surveys / Q000706:statistics & numerical data; D004041:Dietary Fats / Q000008:administration & dosage*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage* / Q000097:blood*; D005260:Female; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage / Q000097:blood; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D012643:Selenium / Q000008:administration & dosage / Q000097:blood
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; D012643:Selenium
keywords: Atypical antipsychotics; Eicosadienoic acid; Hydroperoxy octadecadienoic acid; Omega-3; Omega-6